Hypocholesterolemia in Patients with an Amebic Liver Abscess

BACKGROUND/AIMS: Many parasites induce changes in the lipid profiles of the host. Cholesterol increases the virulence of Entamoeba histolytica in animal models and in vitro culture. This study aimed to determine, in patients with an amebic liver abscess, the correlation between cholesterol and other features, such as the size and number of abscesses, standard hematological and serum chemistry profiles, liver tests, and duration of hospital stay. METHODS: A total of 108 patients with an amebic liver abscess and 140 clinically healthy volunteers were investigated. Cholesterol and triglycerides were measured in the sera. The data from medical observations and laboratory tests were obtained from the clinical records. RESULTS: A total of 93% of patients with an amebic liver abscess showed hypocholesterolemia not related to any of the studied parameters. Liver function tests correlated with the size of the abscess. The most severe cases of amebic liver disease or death were found in patients whose cholesterol levels continued to decrease despite receiving antiamebic treatment and hospital care. CONCLUSIONS: Our results show that the hypocholesterolemia observed in patients with an amebic liver abscess is not related to any of the clinical and laboratory features analyzed. This is the first study relating hypocholesterolemia to severity of hepatic amebiasis.

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.

Padronização de condições experimentais no cultivo e quantificação de Entamoeba histolytica que otimizem ensaios de compostos potencialmente amebicidas / Standardization of experimental conditions in the cultivation and quantification of Entamoeba histolytica that optimize test compounds potentially amebicides

O protozoário, Entamoeba histolytica, constitui a etiologia de milhares de óbitos anuais e, em muitos casos, a falta de saneamento, o grau de instrução e a falta de higiene da população podem favorecer a transmissão e a manutenção desses patógenos em uma comunidade. Por causar tantas mortes e problemas na saúde pública trabalhos que facilitem o estudo deste parasito fazem-se importantes. Uma vez que a padronização de cultivo de E. histolytica em placas de poços vai Existem indicações que mostram que este parasito pode se tornar resistente ao medicamento utilizado no tratamento desta protozoose, por isso, a busca por novas substâncias que possam atuar como tratamento alternativo é de suma importância. Portanto, o objetivo do presente trabalho foi otimizar e padronizar o cultivo e a contagem deste parasito in vitro, além de identificar substâncias com potencial amebicida, que possam ser utilizadas no futuro como fármacos no tratamento da amebíase, sugerindo também uma via possível de ação das substâncias que apresentaram os melhores efeitos. Para tanto, os trofozoítos foram cultivados em placas de 24 poços sobre diferentes condições, quatro métodos de contagem de células foram comparados e 74 (setenta e quatro) substâncias foram testadas. Destas 13 (treze) apresentaram uma inibição na proliferação axênica dos trofozoítos de cerca de 70%. Destas, três compostos foram estudados em mais detalhes, os mesoiônicos derivados da piperina (as MII, MVI e MIX). Estas substâncias pertencem ao grupo dos compostos mesoiônicos, substâncias formadas por um anel heteroatômico composto por nitrogênio, carbono e enxofre, capazes de atravessar membranas e interagir com biomoléculas. Além disso, alguns mesoiônicos são doadores de radicais NO e tais grupamentos são capazes de induzir uma morte celular semelhante à apoptose em E. histolytica, como sugerido pela expressão de fosfatidil-serina revelada por anexina-V. Confirmando os resultados descritos na literatura, estas substâncias foram capazes de induzir uma morte programada, porém observações da ultra-estrutura, tais como figuras de mielina, das células tratadas apontaram para autofagia que também foi evidenciada por testes com MDC gerando apoptose tipo II, que pode ser iniciada pela presença de ROS, que neste caso foram por DCFDA.

A randomized, controlled, open-label trial evaluating the efficacy and safety of chloroquine in the treatment of giardiasis in children / Estudio de etiqueta abierta, randomizado y controlado, para evaluar la eficacia y seguridad de la cloroquina en el tratamiento de la giardiasis en niños

BACKGROUND: Giardia duodenalis is among the commonest protozoan parasites in the intestinal tract of humans and may cause significant morbidity worldwide. Although there are several antigiardial agents, treatment failures have been commonly reported. OBJECTIVE: To compare the efficacy and safety of chloroquine (CQ) versus metronidazole (MTZ) in the treatment of children with confirmed G duodenalis mono-infection. METHODS: A randomized, controlled, open-label trial was carried out at the Cuban Institute of Gastroenterology. One hundred and twenty-two children were randomly assigned to receive either CQ (10 mg/Kg bodyweight twice a day for five days) or MTZ [15 mg/Kg bodyweight divided in three daily does for five days]. All children were asked to provide three faecal samples on days 3, 5 and 7 after treatment completion. Children were considered to be cured, if no Giardia trophozoites or cysts were found in any of the three post-treatment faecal specimens evaluated by direct wet mounts and/or after Ritchie concentration techniques. RESULTS: The frequency of cure was a little higher for CQ than for MTZ but the difference was not statistically significant. Headache was more common in patients treated with CQ as was bitter taste. Yellowish colouration of the urine was more frequent in the MTZ treated group. CONCLUSION: Chloroquine, for five days, is as efficacious as the recommended treatment with MTZ in children infected with G duodenalis.

ANTECEDENTES: La giardia lamblia (giardia duodenalis) se halla entre los parásitos protozoos más comunes del tracto intestinal de los seres humanos, y puede causar una morbilidad significativa a nivel mundial. Aunque existen varios agentes antigiardiales, se han reportado fracasos en el tratamiento OBJETIVO: Comparar la eficacia y seguridad de la cloroquina (CQ) con el metronidazol (MTZ) en el tratamiento de los niños con mono-infección de G duodenalis. MÉTODOS: En el Instituto Cubano de Gastroenterología, se llevó a cabo un estudio de etiqueta abierta, randomizado y controlado. Ciento veintidós niños fueron aleatoriamente designados para recibir bien CQ (10 mg/Kg peso corporal dos veces por día durante cinco días) o MTZ (15 mg/Kg peso corporal dividido en tres dosis diarias por un período de cinco días). A todos los niños se les tomaron tres pruebas fecales los días 3, 5 y 7 después de terminado el tratamiento. Los niños se daban por curados, si no había presencia de tropozoítos o quistes de giardia en ninguno de los tres especimenes fecales post-tratamiento, evaluados directamente con portaobjetos húmedos y/o después de técnicas de concentración de Ritchie. RESULTADO: La frecuencia de la cura fue un poco más alta para CQ que para MTZ, pero la diferencia no fue estadísticamente significativa. El dolor de cabeza fue más común en pacientes tratados con CQ que el sabor amargo. La coloración amarillenta de la orina fue más frecuente en el grupo tratado con MTZ. CONCLUSIÓN: La cloroquina, administrada durante cinco días, es tan eficaz como el tratamiento recomendado con MTZ en niños infectados con giardias lamblias.

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.

Rare presentation of a common disease of tropics.

A 19 years male presented with fever, oliguria and purpuric lesions involving both hands. The patient was diagnosed as a case of purpura fulminans with disseminated intravascular coagulation due to complicated falciparum malaria. The case is presented to sensitize the physicians to keep malaria as a differential in cases of fever with purpura fulminans.

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.

Differentiating amoebic ulcero-haemorrhagic recto-colitis from idiopathic inflammatory bowel disease: still a diagnostic dilemma / Diferenciar la Rectocolitis Úlcero-hemorrágica Amebiana de la Enfermedad Inflamatoria Idiopática del Intestino: un Dilema Diagnóstico sin Resolver

The colon responds monomorphically to a variety of insults thus making it difficult to differentiate invasive amoebic colitis and inflammatory bowel disease (IBD). The authors present a case with chronic dysentery, haematochezia, anaemia and hypoproteinaemia. The endoscopic findings were suggestive of IBD. The stool examination was negative for trophozoites or cysts of parasites. The recto-colonic biopsy specimens showed mucosal inflammation with exudates containing amoebic trophozoites. The patient was successfully treated with metronidazole and iodoquinol. He recovered within two weeks and repeat colonoscopy four weeks after the treatment showed a normal rectum and colon. Clinicians should have a high level of suspicion for amoebic colitis in cases of colitis especially in regions where amoebiasis is still present. Efforts should be made to find the amoebic trophozoites in multiple stool and colonic biopsy specimens

El colon responde de manera monomórfica a una variedad de insultos, lo cual hace difícil distinguir entre la colitis amebiana invasiva y la enfermedad intestinal inflamatoria (EII). Los autores presentan un caso con disentería crónica, hematoquexia, anemia e hipoproteinemia. Los resultados endoscópicos apuntaban a una EII. El análisis de las heces fecales arrojó resultados negativos en cuanto a presencia de trofozoitos o quistes de parásitos. Esto condujo a un diagnóstico erróneo y el paciente fue tratado por una EII. Sin embargo, los especímenes de la biopsia rectocolónica mostraron una inflamación mucosal con exudados en los que se hallaban presentes trofozoitos amebianos. El paciente tuvo un tratamiento exitoso con metronidazol y iodoquinol. Se recuperó en dos semanas, y se le repitió la colonoscopia cuatro semanas después de que el tratamiento mostró un recto y colon normales. Los clínicos debían mostrar un alto nivel de sospecha ante la colitis amebiana, especialmente en aquellas regiones donde la amebiasis todavía está presente. Deben hacerse esfuerzos por encontrar trofozoitos amebianos en múltiples especímenes de heces fecales y biopsia colónica.

Amebiasis in the newborn.

Infestation with Entamoeba histolytica is especially common in areas with low socioeconomic status. Extra intestinal invasive involvement is more frequent in young children with significant mortality. This disease is rarely reported in the newborns. This 19-day-old newborn who was infected with orally given surgar solution is presented. He was successfully treated with omidazole.

Naegleria meningitis: a rare survival.

Acute amebic meningoencephalitis caused by free-living amebae naegleria fowleri is extremely rare and uniformly fatal with only seven survivals reported till date. An interesting case of naegleria meningitis diagnosed by wet mount cytology of cerebrospinal fluid (CSF) and treated with amphoterecin B, rifampicin and ornidazole with complete recovery is presented. In cases of suspected pyogenic meningitis, if CSF staining, antigen detection or culture is negative for bacteria, a wet mount cytology of CSF for naegleria is suggested. Early treatment with amphoterecin B and rifampicin may improve survival.

Tratamento da leishmaniose mucosa com sulfato de aminosidine: resultados de dois anos de acompanhamento / Treatment of mucosal leishmaniasis with aminosidine sulfate: results of two year follow-up

In 1996, 20 of 21 patients with mucosal leishmaniasis, treated in 1994 with aminosidine sulfate, 16mg/kg/day salt, by intramuscular injection for 20 days, were clinically evaluated. One patient died due to disease not related to mucosal leishmaniasis. Seven of 14 patients (66.7% N = 21) who achieved complete remission three months after treatment remained clinically cured 24 months later and seven relapsed in the same period (50% N = 14). Sorological follow-up showed poor correlation with the results of clinical examination.

Em 1996 foram avaliados clinicamente 20 dos 21 pacientes com leishmaniose mucosa, tratados em 1994 com sulfato de aminosidine 16mg do sal/kg/dia, intramuscular, por 20 dias. Um paciente foi a óbito por causas não relacionadas com a leishmaniose mucosa. Dos 14 pacientes (66,7% N = 21) que inicialmente alcançaram a remissão completa dos sinais e sintomas durante os três primeiros meses de seguimento, sete (50% N = 14) permaneceram livres de doença por 24 meses e sete pacientes apresentaram recidiva neste período. O acompanhamento sorológico mostrou pobre correlação com a avaliação clínica.

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).

Comparacion quinfamida vs etofamida en poblacion mexicana con amibiasis intestinal / Comparation of quinfamide vs etofamide in Mexican polulation with intestinal amebiasis

Se llevó a cabo un estudio abierto, comparativo, prospectivo y al azar para evaluar la eficacia y seguridad de la quinfamida y de la etofamida en el tratamiento de pacientes con amibiasis intestinal. Se evaluaron dos poblaciones de niños (1-16 años) y adultos (17-80 años). Las dosis utilizadas fueron: Quinfamida en niños 4.3 mg/Kg 2 veces al día y en adultos 100 mg. cada 8 horas, en ambos por día; y Etofamida en niños 200 mg 3 veces al día y en adultos 500 mg. cada 12 horas, en ambos durante 3 días. Se incluyeron 110 pacientes, 54 en el grupo de la quinafamida y 56 en el de la etofamida. No se observaron diferencias significativas en las características demogr ficas basales. Al finalizar el tratamiento se observó una tasa de curación global para la quinfamida de 87 por ciento y de 76.8 por ciento para la etofamida (p = 0.0696). Separada por poblaciones se mantuvo la diferencia porcentual. Se concluye que la respuesta terapéutica fue mejor para la quinfamida y que el perfil de seguridad de ambos f rmacos es aceptable.

Estudio comparativo entre quinfamida y etofamida en el tratamiento de la infección amibiana asintomática / Comparative study in quinfamide and etofamide in the treatment of asymptomatic amoebic infection

Se realizó un estudio para evaluar la eficacia de la quinfamida y de la etofamida en el tratamiento de la infección amibiana asintomática. Se estudiaron 655 niños con coproparasitoscópicos por concentración en serie de tres días consecutivos. En 501 niños se encontraron quistes de Entamoeba histolytica (76.48 por ciento). Con estos niños de integraron dos grupos, en forma aleatoria; el primero recibió quinfamida y el segundo se le administró etofamida. Se realizaron coproparasitoscópicos al concluir el tratamiento. En el grupo de lka quinfamida se obtuvo una eficacia de 89.3 por ciento y en la etofamida de 89.9 por ciento (p>0.05). Se concluye que la quinfamida y la etofamida son buenas opciones para el manejo del portador sano de Entamoeba histolytica