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Entamoeba histolytica is a disease-causing parasitic amoeba which affects an estimated 50 million people worldwide, particularly in socioeconomically vulnerable populations experiencing water sanitation issues. Infection with E. histolytica is referred to as amoebiasis, and can cause symptoms such as colitis, dysentery, and even death in extreme cases. Drugs exist that are capable of killing this parasite, but they are hampered by downsides such as significant adverse effects at therapeutic concentrations, issues with patient compliance, the need for additional drugs to kill the transmissible cyst stage, and potential development of resistance. Past screens of small and medium sized chemical libraries have yielded anti-amoebic candidates, thus rendering high-throughput screening a promising direction for new drug discovery in this area. In this study, we screened a curated 81,664 compound library from Janssen pharmaceuticals against E. histolytica trophozoites in vitro, and from it identified a highly potent new inhibitor compound. The best compound in this series, JNJ001, showed excellent inhibition activity against E. histolytica trophozoites with EC50 values at 0.29 μM, which is better than the current approved treatment, metronidazole. Further experimentation confirmed the activity of this compound, as well as that of several structurally related compounds, originating from both the Janssen Jump-stARter library, and from chemical vendors, thus highlighting a new structure-activity relationship (SAR). In addition, we confirmed that the compound inhibited E. histolytica survival as rapidly as the current standard of care and inhibited transmissible cysts of the related model organism Entamoeba invadens. Together these results constitute the discovery of a novel class of chemicals with favorable in vitro pharmacological properties. The discovery may lead to an improved therapy against this parasite and in all of its life stages. more...

Entamoeba histolytica is the cause of amoebiasis. The trophozoite (amoeba) form of this parasite is capable of invading the intestine and can disseminate through the bloodstream to other organs. The mechanisms that allow amoebae to evade complement deposition during dissemination have not been well characterized. We previously discovered a novel complement-evasion mechanism employed by E. histolytica. E. histolytica ingests small bites of living human cells in a process termed trogocytosis. We demonstrated that amoebae were protected from lysis by human serum following trogocytosis of human cells and that amoebae acquired and displayed human membrane proteins from the cells they ingested. Here, we aimed to define how amoebae are protected from complement lysis after performing trogocytosis. We found that amoebae were protected from complement lysis after ingestion of both human Jurkat T cells and red blood cells and that the level of protection correlated with the amount of material ingested. Trogocytosis of human cells led to a reduction in deposition of C3b on the surface of amoebae. We asked whether display of human complement regulators is involved in amoebic protection, and found that CD59 was displayed by amoebae after trogocytosis. Deletion of a single complement-regulatory protein, CD59 or CD46, from Jurkat cells was not sufficient to alter amoebic protection from lysis, suggesting that multiple, redundant complement regulators mediate amoebic protection. However, exogeneous expression of CD46 or CD55 in amoebae was sufficient to confer protection from lysis. These studies shed light on a novel strategy for immune evasion by a pathogen. IMPORTANCE Entamoeba histolytica is the cause of amoebiasis, a diarrheal disease of global importance. While infection is often asymptomatic, the trophozoite (amoeba) form of this parasite is capable of invading and ulcerating the intestine and can disseminate through the bloodstream to other organs. Understanding how E. histolytica evades the complement system during dissemination is of great interest. Here, we demonstrate for the first time that amoebae that have performed trogocytosis (nibbling of human cells) resist deposition of the complement protein C3b. Amoebae that have performed trogocytosis display the complement-regulatory protein CD59. Overall, our studies suggest that acquisition and display of multiple, redundant complement regulators is involved in amoebic protection from complement lysis. These findings shed light on a novel strategy for immune evasion by a pathogen. Since other parasites use trogocytosis for cell killing, our findings may apply to the pathogenesis of other infections. more...

Chronic diarrhea, characterized by the presence of more than three loose stools for at least four weeks, is often found in clinical practice. In chronic diarrhea, the probability of an infectious etiology is low, having usually a functional, inflammatory, osmotic or secretory origin. Intestinal amebiasis is a cause of chronic diarrhea, caused by the protozoan Entamoeba histolytica, common and prevalent in developing countries. It can have different presentations but most patients are asymptomatic. We present a 27-year-old Caucasian male, man who have sex with men (MSM), with chronic diarrhea starting six years ago. The physical exam was normal. A parasitological stool examination was performed with isolation of cysts of Entamoeba histolytica. He was treated with metronidazole and paromomycin with clinical resolution. It is important for General Practice to address this etiology in the investigation of patients with diarrhea for a correct and timely diagnosis and treatment, to avoid unnecessary testing, possible complications, transmission of the agent and a serious public health problem. La diarrea crónica, caracterizada por la presencia de más de tres heces de consistencia blanda durante al menos cuatro semanas, es frecuentemente encontrada en la práctica clínica. En la diarrea crónica, la probabilidad de una etiología infecciosa es baja, siendo las causas funcionales, inflamatorias, osmóticas o secretoras más comunes. La amebiasis intestinal es una causa de diarrea crónica, causada por el protozoario Entamoeba histolytica, siendo común y prevalente en los países en desarrollo. Puede tener varias formas de presentación, siendo en la mayoría de los casos asintomática. Presentamos un paciente de 27 años, sexo masculino, caucásico, hombre que tiene sexo con hombres (HSH), con diarrea crónica con inicio hacecerca de seis años. El examen objetivo no reveló alteraciones. Realizó un examen parasitológico de heces, con aislamiento de quistes de Entamoeba histolytica. Fue medicado con metronidazol y paromomicina con resolución clínica del cuadro. Es importante para el médico de familia considerar esta etiología en la investigación de pacientes con diarrea, para un correcto y oportuno diagnóstico y tratamiento, de modo a evitar, exámenes innecesarios, posibles complicaciones, la transmisión del agente y un grave problema de salud pública. A diarreia crônica, caracterizada pela presença de mais de três dejeções de consistência pastosa durante pelo menos quatro semanas, é frequentemente encontrada na prática clínica. Na diarreia crônica, a probabilidade de uma etiologia infecciosa é baixa, sendo as causas funcionais, inflamatórias, osmóticas ou secretórias mais comuns. A amebíase intestinal é uma causa de diarreia crônica, causada pelo protozoário Entamoeba histolytica, sendo comum e prevalente em países em desenvolvimento. Pode ter várias formas de apresentação, sendo na maioria dos casos assintomática. Apresenta-se o caso clínico de um paciente de 27 anos, sexo masculino, raça caucasiana, homem que pratica sexo com homens (HSH), com diarreia crônica com início há cerca de seis anos. O exame objetivo não revelava alterações. Realizou exame parasitológico de fezes, com isolamento de quistos de Entamoeba histolytica. Foi medicado com metronidazol e paromomicina com resolução clínica do quadro. É importante para o Médico de Família equacionar esta etiologia na investigação de pacientes com diarreia, para um correto e atempado diagnóstico e tratamento, de modo a evitar exames desnecessários, possíveis complicações, a transmissãodo agente e um grave problema de saúde pública. more...

The lack of sanitation and poor access to health services favor polyparasitism, contributing to delayed cognitive and physical development of children or evolution to complications that endanger their health. This study reports a complication of liver abscess in a three-years-old child with polyparasitism from a riverside community, and discusses the sanitation conditions and health care access of this population. During the child’s hospitalization, data were obtained from the multidisciplinary team, medical records, and the family. Literature data are consistent with this report showing that, despite the measures taken to increase access to health care, communities underserved by the local government still exist. Further studies to know the profile of this population and the implementation of public policies aiming to improve the quality of life with lower costs in the long term, are still necessary. La falta de saneamiento básico y las dificultades en el acceso a los servicios de salud favorecen el poliparasitismo, contribuyendo al retraso en el desarrollo cognitivo y físico de los niños, o bien a su evolución, con complicaciones que ponen en peligro su salud. Se presenta aquí una complicación de absceso hepático en una niña de tres años con poliparasitismo desde una comunidad ribereña, y se discute acerca de las condiciones de saneamiento y acceso a los servicios de salud de esta población. Los datos se obtuvieron junto al equipo multidisciplinario participante durante la hospitalización, de los registros médicos y de los familiares. Los datos de la literatura son compatibles con el caso y muestran, que aunque haya mejoras en el acceso a los servicios de salud en algunas comunidades, todavía quedan comunidades desatendidas por el gobierno, lo que exige más estudios para conocer el perfil de esta población y implementar políticas públicas que mejoren la calidad de vida, con menores costos y a largo plazo. A falta de saneamento básico e as dificuldades de acesso aos serviços de saúde favorecem o poliparasitismo, contribuindo para retardo no desenvolvimento cognitivo e físico de crianças ou evolução com complicações que colocam em risco sua saúde. Relata-se aqui uma complicação de abscesso hepático em criança de três anos, poliparasitada, proveniente de comunidade ribeirinha, e discute-se sobre as condições de saneamento e acesso à saúde dessa população. Os dados foram obtidos junto à equipe multiprofissional envolvida durante a internação, ao prontuário e familiares. Dados da literatura são compatíveis com o relato ao mostrarem que, apesar das medidas de ampliação do acesso à saúde via fluvial e da melhoria sanitária em algumas comunidades, ainda há locais desassistidos pelo poder público, sendo necessária a realização de mais estudos para o conhecimento do perfil dessa população e a implantação de políticas públicas que visem melhorar a qualidade de vida, com menores custos em longo prazo. more...

El absceso hepático (AH) sigue siendo causa de alta morbilidad y mortalidad en el mundo. OBJETIVO: Conocer las características demográficas, presentación clínico - imagenológica y manejo en el Hospital Nacional Arzobispo Loayza en 5 años. MÉTODOS: Estudio descriptivo - retrospectivo, basado en la revisión de historias clínicas de pacientes con diagnóstico de AH entre Enero 2003 a Diciembre 2007. RESULTADOS: De 106 historias clínicas revisadas, 46 ingresaron al estudio. La edad media fue de 47,8 años (95% IC 41,9-53,8 años), 21 pacientes eran mayores de 50 años (45,6%) y 52,2% fueron varones. Los síntomas principales fueron fiebre (95,6%) y dolor en hipocondrio derecho (73,5%); el tiempo promedio de enfermedad fue 2,5 semanas. Encontramos elevada frecuencia de hipoalbuminemia, incremento de fosfatasa alcalina, leucocitosis y anemia. El diagnóstico principalmente fue ecográfico (97,8%), como absceso único (73%), ubicado en lóbulo derecho (77%), con un diámetro promedio de 70mm (p25-75: 44-90mm) y 69,6% tuvieron más de 5 cm de diámetro. Todos recibieron antibioticoterapia por 18,6 días en promedio (rango: 3-30); siendo la combinación más frecuente metronidazol y ciprofloxacino. Diecisiete pacientes (36,9%) fueron operados, 7 pacientes (15,2%) recibieron drenaje externo con catéter percutáneo y en 10,9% (5 pacientes) se manejó con aspiración directa. CONCLUSIÓN: El AH es una patología aguda o subaguda, de mediana edad, sin preferencia de género, cuya sintomatología principal es fiebre y dolor en hipocondrio derecho. Es necesario protocolizar el manejo de esta patología. The liver abscess (LA) continues to cause a high morbidity and mortality worldwide. OBJETIVES: To determine demographic characteristics, clinical presentation, Imaging and management at the Arzobispo Loayza Hospital in 5 years. METHODS: A descriptive retrospective study, based on medical records of patients diagnosed with LA between January 2003 to December 2007. RESULTS: Of 106 medical records reviewed, 46 entered the study. The mean age was 47.8 years (95% CI 41.9-53.8 years), 21 patients were over 50 years (45.6%) and 52.2% were male. The main symptoms were fever (95.6%) and right upper quadrant pain (73.5%). The average time of disease was 2.5 weeks. We found high frequency of hypoalbuminemia, elevated alkaline phosphatase, leukocytosis and anemia. The diagnosis was mostly based on ecography (97.8%), AH were mainly a single abscess (73%) located in the right lobe (77%), with an average diameter of 70 mm (p25-75: 44-90mm), and 69.6% had more than 5 cm in diameter. Antibiotics were administered for 18.6 days (range: 3-30), being the combination administered more frequently metronidazole and ciprofloxacin. Seventeen patients (36.9%) underwent surgery, 7 patients (15.2%) received external drainage by percutaneous catheter and 10.9% (5 patients) was aspirated directly. CONCLUSION: LA is an acute or subacute disease of middle age without gender bias, whose main symptoms are fever and right upper quadrant pain. It is necessary to protocolize the management of this condition. more...

Background: Amebic colitis although common, rarely presents as fulminant colitis which has a high morbidity and mortality unless treated promptly and appropriately. Aim: To study the clinical, morphological features and outcome of fulminant amebic colitis (FAC). Materials and m0 ethods: A retrospective study of six patients who underwent surgical resections from 2002-06 and were diagnosed with FAC, was carried out. The morphological features assessed included the average number of trophozoites per high-power field and the depth of invasion of trophozoites into the muscularis propria. Results: The study included five adults and one child who underwent surgery for fulminant colitis. Interestingly, a definite preoperative diagnosis of amebic colitis was made only in one patient and suspected in another. Intraoperatively, multiple perforations of the intestine with peritonitis were the most common findings. Gross examination typically revealed multiple ulcers with exudate and intervening normal mucosa. Microscopically, ulceration and myonecrosis with trophozoites within the exudate were seen in all cases. Trophozoites invading the muscularis propria were seen in five cases. Of the cases that showed myoinvasion by trophozoites, two patients expired within two weeks of surgery. One of the patients who expired also showed co-infection with Actinomyces. Conclusion: FAC is an uncommon outcome in amebic colitis with a high mortality requiring prompt surgical intervention. more...

La infección por Entamoeba histolytica puede causar disentería y absceso hepático amebiano, enfermedades de alta morbi-mortalidad. Los estudios seroepidemiológicos han demostrado que la mayoría (81-100%) de los pacientes con absceso hepático amebiano y hasta la mitad en la colitis amebiana desarrollan inmunoglobulina G (IgG) específica para E. histolytica, que persiste por varios años. Por tal motivo, hay controversia acerca de la utilidad de la prueba de ELISA IgG para el diagnóstico de absceso hepático amebiano en países tropicales, donde se ha reportado una alta prevalencia de la enfermedad. Se presenta el seguimiento, durante 32 meses, mediante IgG de un paciente de 69 años, proveniente del Chocó en Colombia, con diagnóstico de absceso hepático amebiano, comprobado mediante ecografía, ELISA para IgG, e inmunodifusión y por la respuesta al tratamiento con metronidazol. Las pruebas inmunodiagnósticas han permanecido positivas durante el seguimiento. Entamoeba histolytica causes dysentery and amebic liver abscess diseases, with high morbid and mortality. Seroepidemiological surveys have shown that 81-100% of patients with amebic liver abscess and 50% of patients with amebic colitis developed specific anti-E. histolytica IgG antibodies which may persist for several years. For this reason the usefulness of the ELISA test for IgG antibodies in amebic liver abscess diagnosis has been questioned in tropical countries where prevalence of the disease is high. This paper presents the follow-up during 32 months of the IgG antibodies in a 69 year old patient from Chocó (Colombia), with one amebic liver abscess confirmed by liver ultrasound, ELISA IgG and inmunodifution, who response to treatment with metronidazole. The immunodiagnostic tests have been consistently positive during follow-up. more...

Background: The non invasive diagnosis of amebic liver abscess allows the use of empirical therapy without the requirement of invasive diagnostic procedures. Aim: To determine the discriminatory capacity of clinical, laboratory and ultrasound studies for the etiological diagnosis of liver abscess. Patients and methods: Sixty one patients were initially included in this prospective study, but 12 did not comply with the inclusion criteria. Of the rest, 29 (59%) had an amebic liver abscess, 16 (33%) had a pyogenic liver abscess and four (8%) had an abscess of mixed etiology. Blood cultures were done in 42 patients. Ultrasound guided needle aspiration was done in 7 patients with amebic liver abscess and 13 patients with non amebic liver abscess. Results: The clinical picture and ultrasound fndings were similar in all types of amebic abscess. ELISA test for IgG anti-Entamoeba histolytica antibodies were positive in 100% of patients with amebic liver abscess. Antibodies measured by gel diffusion were positive in 93%. All patients with mixed liver abscess had positive antibodies and some of them positive culture. Blood cultures were positive for anaerobic bacteria in five patients. Cultures of aspirated material were positive in 7 patients (obligate anaerobic bacteria in 3 and facultative anaerobic bacteria in the rest). The most common complications, whatever the etiology, were right pleural effusion and systemic inflammatory response. Conclusions: A final model of binomial regression analysis revealed that age under 40 years, an hematocrit greater than 35% and an elevation in prothrombin time of less than 1.5 seconds had enough discriminatory capacity for the diagnosis of amoebic liver abscess (Rev Méd Chile 2003; 131: 1411-20). more...

Background: The non invasive diagnosis of amebic liver abscess allows the use of empirical therapy without the requirement of invasive diagnostic procedures. Aim: To determine the discriminatory capacity of clinical, laboratory and ultrasound studies for the etiological diagnosis of liver abscess. Patients and methods: Sixty one patients were initially included in this prospective study, but 12 did not comply with the inclusion criteria. Of the rest, 29 (59%) had an amebic liver abscess, 16 (33%) had a pyogenic liver abscess and four (8%) had an abscess of mixed etiology. Blood cultures were done in 42 patients. Ultrasound guided needle aspiration was done in 7 patients with amebic liver abscess and 13 patients with non amebic liver abscess. Results: The clinical picture and ultrasound fndings were similar in all types of amebic abscess. ELISA test for IgG anti-Entamoeba histolytica antibodies were positive in 100% of patients with amebic liver abscess. Antibodies measured by gel diffusion were positive in 93%. All patients with mixed liver abscess had positive antibodies and some of them positive culture. Blood cultures were positive for anaerobic bacteria in five patients. Cultures of aspirated material were positive in 7 patients (obligate anaerobic bacteria in 3 and facultative anaerobic bacteria in the rest). The most common complications, whatever the etiology, were right pleural effusion and systemic inflammatory response. Conclusions: A final model of binomial regression analysis revealed that age under 40 years, an hematocrit greater than 35% and an elevation in prothrombin time of less than 1.5 seconds had enough discriminatory capacity for the diagnosis of amoebic liver abscess (Rev Méd Chile 2003; 131: 1411-20). more...

Liver abscesses are a rare disease with 80-100% mortality in untreated cases. The advent of ultrasound in the clinical practice has improved the prognosis. Surgery for this disease has a percentage of complications of 15-52% and a mortality of 12-33%. In a review of the literature about 200 liver abscesses treated with ultrasound-guided percutaneous drainage the complications were 7.5% and the mortality was 3%. The authors report their personal experience about 21 hepatic abscesses in 13 patients. Nineteen abscesses were treated with ultrasound-guided percutaneous drainage and two with antibiotics. Six patients had pyogenic liver abscesses, two amebic and in five patients the cultures were sterile. In 9 cases the location was in the right lobe of the liver, in 3 was in the left lobe. One patient had multiple abscesses. The size of the abscesses ranged from 0.5 to 13 cm. We drained with Seldinger technique or direct procedure with Trocar's needle under ultrasound guidance without serious complications and without mortality. In 6 cases the patients had pain during the procedure and in 3 cases medical therapy was necessary. In one case we had a pleuritis for the puncture of costophrenic space. All the patients treated had a complete resolution of the abscesses. The ultrasound-guided percutaneous drainage is the treatment of choice for liver abscesses. But other reports with more patients are necessary to clarify the indications and the ultrasound criteria of recovery. more...