Anti-echinococcal effect of metformin in advanced experimental cystic echinococcosis: reprogrammed intermediary carbon metabolism in the parasite.

Metformin, a safe biguanide derivative with antiproliferative properties, has shown antiparasitic efficacy against the Echinococcus larval stage. Hence, we assessed the efficacy of a dose of 250 mg kg-1 day-1 in experimental models of advanced CE, at 6 and 12 months post-infection with oral and intraperitoneal administration, respectively. At this high dose, metformin reached intracystic concentrations between 0.7 and 1.7 mM and triggered Eg-TOR inhibition through AMPK activation by AMP-independent and -dependent mechanisms, which are dependent on drug dose. Cystic metformin uptake was controlled by increased expression of organic cation transporters in the presence of the drug. In both experimental models, metformin reduced the weight of parasite cysts, altered the ultrastructural integrity of their germinal layers, and reduced the intracystic availability of glucose, limiting the cellular carbon and energy charge and the proliferative capacity of metacestodes. This glucose depletion in the parasite was associated with a slight increase in cystic uptake of 2-deoxiglucose and the transcriptional induction of GLUT genes in metacestodes. In this context, drastic glycogen consumption led to increased lactate production and altered intermediary metabolism in treated metacestodes. Specifically, the fraction of reducing soluble sugars decreased twofold, and the levels of non-reducing soluble sugars, such as sucrose and trehalose, were modified in both cystic fluid and germinal cells. Taken together, our findings highlight the relevance of metformin as a promising candidate for CE treatment and warrant further research to improve the therapeutic conditions of this chronic zoonosis in humans.

Follow up study of symptomatic human cystic echinococcosis treatment with albendazole and praziquantel, in Uruguay.

BACKGROUND: Cystic echinococcosis (CE) is a chronic disease considered a neglected one. Cystic echinococcosis is endemic in Uruguay and the region. Surgery, using various technical approaches, has the potential to safely remove the cyst(s) and lead to a complete cure in a high number of patients with simple forms of CE. However, surgery may be impractical in patients with multiple cysts in several organs, high surgical risk, or in patients with previous multiple surgeries. In these cases, the pharmacological treatment with the benzimidazolic drug Albendazole (ABZ) alone or combined with Praziquantel (PZQ), has been promising as the best choice to achieve improvement or cure. METHODS: In this study, we analyze the results obtained on the anti-parasitic treatment of 43 patients diagnosed with CE between the years 2003 and 2020. Patients were treated before and/or after surgery with ABZ or the combination ABZ/PZQ. The standardize protocol of the anti-parasitic drug treatment before surgery was 7 days, 15 days or 1 month depending on the urgency and availability of the surgical procedure. All cases that involved confirmed locations on lungs underwent immediate surgery with minimal pre-treatment when possible. After surgery, the standardize protocol of anti-parasitic drug treatment consisted of six cycles of 30 days each and resting intervals of 15 days in between. ABZ was used in all cases, administered orally, twice daily, at a total dosage of 15 mg/kg/day, with food high in fat content for improved absorption. The follow up was carried out according to WHO-IWGE guidelines for 5 years. RESULTS: Of the 43 patients fourteen were ≤ 15 years of age and had a differentiated pre-surgical treatment. From the ≥ 16 years of age, 36 completed the treatments and the 5 years follow up. Four patients changed geographical locations, without a forwarding contact, after the post-surgery treatment. No patient died during the study. Of the 36 patients that completed the study, 32 were treated only with ABZ; 93.75% achieved treatment success as determined by improvement or cure, and 6.25% treatment failure determined by no change or worsening. The last four patients received the ABZ/PZQ combination therapy and achieved 100% treatment success. CONCLUSION: The pharmacological treatment resulted in a good option not only as palliative but also as potentially curative. The main relevance of its use was in cases with previous multiple surgeries or surgeries with potential life-threatening complications due to the number and location of cysts and concurrent comorbidities. A follow-up of at least 5 years would be recommended to assure remission and control of the transmission. More randomized trials are needed to provide clear clinical evidence of different pharmacological treatments for CE.

Characterization of protein cargo of Echinococcus granulosus extracellular vesicles in drug response and its influence on immune response.

BACKGROUND: The Echinococcus granulosus sensu lato species complex causes cystic echinococcosis, a zoonotic disease of medical importance. Parasite-derived small extracellular vesicles (sEVs) are involved in the interaction with hosts intervening in signal transduction related to parasite proliferation and disease pathogenesis. Although the characteristics of sEVs from E. granulosus protoscoleces and their interaction with host dendritic cells (DCs) have been described, the effect of sEVs recovered during parasite pharmacological treatment on the immune response remains unexplored. METHODS: Here, we isolated and characterized sEVs from control and drug-treated protoscoleces by ultracentrifugation, transmission electron microscopy, dynamic light scattering, and proteomic analysis. In addition, we evaluated the cytokine response profile induced in murine bone marrow-derived dendritic cells (BMDCs) by qPCR. RESULTS: The isolated sEVs, with conventional size between 50 and 200 nm, regardless of drug treatment, showed more than 500 cargo proteins and, importantly, 20 known antigens and 70 potential antigenic proteins, and several integral-transmembrane and soluble proteins mainly associated with signal transduction, immunomodulation, scaffolding factors, extracellular matrix-anchoring, and lipid transport. The identity and abundance of proteins in the sEV-cargo from metformin- and albendazole sulfoxide (ABZSO)-treated parasites were determined by proteomic analysis, detecting 107 and eight exclusive proteins, respectively, which include proteins related to the mechanisms of drug action. We also determined that the interaction of murine BMDCs with sEVs derived from control parasites and those treated with ABZSO and metformin increased the expression of pro-inflammatory cytokines such as IL-12 compared to control cells. Additionally, protoscolex-derived vesicles from metformin treatments induced the production of IL-6, TNF-α, and IL-10. However, the expression of IL-23 and TGF-ß was downregulated. CONCLUSIONS: We demonstrated that sEV-cargo derived from drug-treated E. granulosus protoscoleces have immunomodulatory functions, as they enhance DC activation towards a type 1 pro-inflammatory profile against the parasite, and therefore support the proposal of a new approach for the prevention and treatment of secondary echinococcosis.

Hidatidosis subcutánea primaria / Primary subcutaneous hydatid disease: a case report

La hidatidosis o equinococosis quística es una zoonosis parasitaria endémica causada por el estadio larvario del cestode Echinococcus granulosus. El hígado y el pulmón son los órganos con afección más frecuente. Su ubicación subcutánea es una entidad rara, poco descrita, y por ende un reto diagnóstico. Describimos el caso de una mujer, de 18 años de edad, procedente de un área endémica, que presentó un quiste hidatídico primario supraclavicular.

Hydatid disease or cystic echinococcosis is an endemic parasitic zoonosis caused by the larval stage of the cestode Echinococcus granulosus, the liver and lung being the most frequently affected organs. Its subcutaneous location is a rare entity, little described, and therefore a diagnostic challenge. We describe the case of an 18-year-old woman from an endemic area who presented with a primary supraclavicular hydatid cyst.

Disseminated Abdominal Echinococcosis: Case Report / Equinococosis abdominal diseminada: reporte de caso

Abstract We describe a case of disseminated abdominal hydatid disease in a 21-year-old man who presented with clinical symptoms of persistent abdominal pain after abscess drainage post-appendectomy. The images showed multiple cystic lesions in the peritoneum, liver, and spleen. Due to pain exacerbation, the patient was taken to laparotomy. Multiple cystic lesions scattered throughout the abdominal cavity were observed, which were diagnosed by histopathology as multiple cystic lesions due to peritoneal and abdominal echinococcosis.

Resumen Se realiza la descripción de un caso de hidatidosis abdominal diseminada de un hombre de 21 años, quien consultó por cuadro clínico de dolor abdominal persistente después de un drenaje de absceso luego de una apendicetomía. Las imágenes mostraron múltiples lesiones quísticas en peritoneo, hígado y bazo. Por exacerbación del dolor, el paciente se lleva a laparotomía, donde se evidenciaron múltiples lesiones quísticas diseminadas en toda la cavidad abdominal, que se diagnosticaron a la histopatología como lesiones quísticas múltiples por equinococosis peritoneal y abdominal.

Metformin improves the therapeutic efficacy of low-dose albendazole against experimental alveolar echinococcosis.

Alveolar echinococcosis (AE) is a severe disease caused by Echinococcus multilocularis. Its chemotherapeutic treatment is based on benzimidazoles, which are rarely curative and cause several adverse effects. Therefore, it is necessary to develop alternative and safer chemotherapeutic strategies against AE. It has previously been shown that metformin (Met) exhibits considerable in vivo activity on an early-infection model of AE when administered at 50 mg kg−1 day−1 for 8 weeks. Here, the challenge is heightened by a 2-fold increase in parasite inoculum or by starting the treatment 6 weeks post-infection. In both cases, only the combination of Met (100 mg kg−1 day−1) together with a sub-optimal dose of albendazole (ABZ) (5 mg kg−1 day−1) led to a significant reduction in parasite weight compared to the untreated group. Coincidentally, drug combination showed the highest level of damage in E. multilocularis metacestodes. Likewise, Met alone or combined with ABZ led to a decrease in parasite glucose availability, which was evidenced as a lower intracystic glucose concentration. Therefore, the results demonstrate that combination therapy with Met and ABZ offers an alternative to improve the efficacy and reduce the toxicity of the high-dose ABZ monotherapy currently employed.

The combination of carvacrol and albendazole enhanced the efficacy of monotherapy in experimental alveolar echinococcosis.

Alveolar echinococcosis is a helminthic zoonosis caused by the larval stage of Echinococcus multilocularis. When surgical resection of the parasite is not feasible, pharmacological treatment with albendazole is the only option. Due to the difficulties in achieving the success of treatment, it is necessary to find new drugs to improve the treatment of this disease. In the present work, the efficacy of carvacrol alone or combined with albendazole was evaluated against E. multilocularis metacestodes. The association of carvacrol with albendazole produced a greater in vitro effect than the compounds incubated separately. The most effective treatment was the combination of 10 µg/ml of carvacrol and 1 µg/ml of albendazole. In the clinical efficacy study, treatment of infected mice with carvacrol (40 mg/kg) and albendazole (25 mg/kg) reduced the weight of metacestodes by 29 % and 50 %, respectively; while the combination of drugs had an efficacy of 83 %. These results coincided with the tissue damage observed at the ultrastructural level. In conclusion, carvacrol and albendazole combination enhanced the efficacy of monotherapy. This strategy would allow to improve the efficacy of the treatment without increasing the doses of albendazole or lengthen the treatment period, reducing the occurrence of adverse effects.

Case Report: Total Nephrectomy for Renal Hydatidosis.

Cystic echinococcosis, known as hydatidosis, is a parasitic zoonosis caused by the larvae of Echinococcus granulosus. Renal hydatidosis is a very rare condition, representing 1% to 2% of cases. We present an 18-year-old patient who, after suffering a trauma, experienced severe lower back pain and persistent gross hematuria disproportionate to the trauma. Ultrasonography and tomography revealed cystic images compatible with right renal hydatidosis and hemoperitoneum. In addition, rapid clinical deterioration was observed with decreased hematocrit, leading to lumpectomy with abundant cysts inside and outside the right kidney, without viable parenchyma. Therefore, a total nephrectomy was performed. The patient was discharged with albendazole treatment. Pathological anatomic analysis confirmed the diagnosis of hydatidosis. Surgery remains the best therapeutic option. The use of ultrasonography improves the early detection of zoonosis, especially in pediatric patients, and favors the use of more conservative therapeutic techniques.

Expression profiling of Echinococcus multilocularis miRNAs throughout metacestode development in vitro.

The neglected zoonotic disease alveolar echinococcosis (AE) is caused by the metacestode stage of the tapeworm parasite Echinococcus multilocularis. MicroRNAs (miRNAs) are small non-coding RNAs with a major role in regulating gene expression in key biological processes. We analyzed the expression profile of E. multilocularis miRNAs throughout metacestode development in vitro, determined the spatial expression of miR-71 in metacestodes cultured in vitro and predicted miRNA targets. Small cDNA libraries from different samples of E. multilocularis were sequenced. We confirmed the expression of 37 miRNAs in E. multilocularis being some of them absent in the host, such as miR-71. We found a few miRNAs highly expressed in all life cycle stages and conditions analyzed, whereas most miRNAs showed very low expression. The most expressed miRNAs were miR-71, miR-9, let-7, miR-10, miR-4989 and miR-1. The high expression of these miRNAs was conserved in other tapeworms, suggesting essential roles in development, survival, or host-parasite interaction. We found highly regulated miRNAs during the different transitions or cultured conditions analyzed, which might suggest a role in the regulation of developmental timing, host-parasite interaction, and/or in maintaining the unique developmental features of each developmental stage or condition. We determined that miR-71 is expressed in germinative cells and in other cell types of the germinal layer in E. multilocularis metacestodes cultured in vitro. MiRNA target prediction of the most highly expressed miRNAs and in silico functional analysis suggested conserved and essential roles for these miRNAs in parasite biology. We found relevant targets potentially involved in development, cell growth and death, lifespan regulation, transcription, signal transduction and cell motility. The evolutionary conservation and expression analyses of E. multilocularis miRNAs throughout metacestode development along with the in silico functional analyses of their predicted targets might help to identify selective therapeutic targets for treatment and control of AE.

Quiste hidático primario músculo-esquelético: revisión de la literatura a propósito de un caso / Primary hydatid cyst of skeletal muscle: a literature review based on a case / Cisto hidático primário músculo esquelético: revisão da literatura a propósito de um caso

Resumen: Introducción: la equinococosis quística músculo-esquelética es poco frecuente, pudiendo determinar retrasos diagnósticos y errores terapéuticos. Reporte de caso: presentamos el caso de un paciente con un quiste hidático primario único a nivel de la región femoral posterior derecha, infectado. Discusión: se realizó una revisión en las bases de datos PubMed y LILACS sobre el diagnóstico y manejo terapéutico de los quistes hidáticos músculo-esqueléticos primarios. Conclusiones: la equinococosis quística músculo-esquelética debe ser tenida en cuenta dentro de los diagnósticos diferenciales de tumoraciones de partes blandas en pacientes provenientes de zonas endémicas. La tomografía computada y/o resonancia magnética cumplen un rol diagnóstico y de planificación terapéutica. El tratamiento es quirúrgico, a medida del paciente y del quiste, en función de su topografía, tamaño y fundamentalmente relaciones vasculo nerviosas y musculares. Otros factores a tener en cuenta son las futuras secuelas funcionales y resultados estéticos.

Summary: Introduction: musculoskeletal cystic echinococcosis is rather an unusual condition, what may result in delayed diagnosis and therapeutic mistakes. Case report: the study presents the case of a patient with a single primary hydatid cyst in the right posterior femoral region, which is infected. Discussion: a review of PubMed and LILACS was performed to learn about diagnosis and therapeutic handling of the primary musculoskeletal hydatid cysts. Conclusions: musculoskeletal cystic echinococcosis needs to be considered among differential diagnosis of soft tissues tumors in patients coming from endemic areas. A CT scan and RMI play an important role in diagnosis and the planning of treatment. Treatment involves surgery that must be adapted to the patient and the cyst, considering its topography and size, and in particular in view of muscular and nervous vessels relationship. Other factors to bear in mind are renal sequels and esthetic aspects.

Resumo: Introdução: a equinococose cística musculoesquelética é rara e pode determinar atrasos em seu diagnóstico e erros terapêuticos. Relato do caso: apresentamos o caso de uma paciente com cisto hidrático primário único ao nível da região femoral posterior direita, infectado. Discussão: foi realizada uma revisão nas bases de dados PubMed e LILACS sobre o diagnóstico e manejo terapêutico dos cistos hidráticos osteomusculares primários. Conclusões: a equinococose cística musculoesquelética deve ser considerada no diagnóstico diferencial de tumores de partes moles em pacientes de áreas endêmicas. A tomografia computadorizada e / ou a ressonância magnética desempenham um papel no planejamento diagnóstico e terapêutico. O tratamento é cirúrgico, adaptado ao paciente e ao cisto, dependendo de sua topografia, tamanho e, fundamentalmente, das relações vascular-nervosas e musculares. Outros fatores a serem considerados são as sequelas funcionais futuras e os resultados estéticos.

Application of target repositioning and in silico screening to exploit fatty acid binding proteins (FABPs) from Echinococcus multilocularis as possible drug targets.

Fatty acid binding proteins (FABPs) are small intracellular proteins that reversibly bind fatty acids and other hydrophobic ligands. In cestodes, due to their inability to synthesise fatty acids and cholesterol de novo, FABPs, together with other lipid binding proteins, have been proposed as essential, involved in the trafficking and delivery of such lipophilic metabolites. Pharmacological agents that modify specific parasite FABP function may provide control of lipid signalling pathways, inflammatory responses and metabolic regulation that could be of crucial importance for the parasite development and survival. Echinococcus multilocularis and Echinococcus granulosus are, respectively, the causative agents of alveolar and cystic echinococcosis (or hydatidosis). These diseases are included in the World Health Organization's list of priority neglected tropical diseases. Here, we explore the potential of FABPs from cestodes as drug targets. To this end, we have applied a target repurposing approach to identify novel inhibitors of Echinococcus spp. FABPs. An ensemble of computational models was developed and applied in a virtual screening campaign of DrugBank library. 21 hits belonging to the applicability domain of the ensemble models were identified, and 3 of the hits were assayed against purified E. multilocularis FABP, experimentally confirming the model's predictions. Noteworthy, this is to our best knowledge the first report on isolation and purification of such four FABP, for which initial structural and functional characterization is reported here.

Metformin Suppresses Development of the Echinococcus multilocularis Larval Stage by Targeting the TOR Pathway.

Alveolar echinococcosis (AE) is a severe disease caused by the larval stage of the tapeworm Echinococcus multilocularis Current chemotherapeutic treatment options based on benzimidazoles are of limited effectiveness, which underlines the need to find new antiechinococcosis drugs. Metformin is an antihyperglycemic and antiproliferative agent that shows activity against the related parasite Echinococcus granulosus Hence, we assessed the in vitro and in vivo effects of the drug on E. multilocularis Metformin exerted significant dose-dependent killing effects on in vitro cultured parasite stem cells and protoscoleces and significantly reduced the dedifferentiation of protoscoleces into metacestodes. Likewise, oral administration of metformin (50 mg/kg of body weight/day for 8 weeks) was effective in achieving a significant reduction of parasite weight in a secondary murine AE model. Our results revealed mitochondrial membrane depolarization, activation of Em-AMPK, suppression of Em-TOR, and overexpression of Em-Atg8 in the germinal layer of metformin-treated metacestode vesicles. The opposite effects on the level of active Em-TOR in response to exogenous insulin and rapamycin suggest that Em-TOR is part of the parasite's insulin signaling pathway. Finally, the presence of the key lysosomal pathway components, through which metformin reportedly acts, was confirmed in the parasite by in silico assays. Taken together, these results introduce metformin as a promising candidate for AE treatment. Although our study highlights the importance of those direct mechanisms by which metformin reduces parasite viability, it does not necessarily preclude any additional systemic effects of the drug that might reduce parasite growth in vivo.

Drug repurposing for the treatment of alveolar echinococcosis: in vitro and in vivo effects of silica nanoparticles modified with dichlorophen.

Alveolar echinococcosis is a neglected parasitic zoonosis caused by the metacestode Echinococcus multilocularis, which grows as a malignant tumour-like infection in the liver of humans. Albendazole (ABZ) is the antiparasitic drug of choice for the treatment of the disease. However, its effectiveness is low, due to its poor absorption from the gastro-intestinal tract. It is also parasitostatic and in some cases produces side-effects. Therefore, an alternative to the treatment of this severe human disease is necessary. In this context, the repositioning of drugs combined with nanotechnology to improve the bioavailability of drugs emerges as a useful, fast and inexpensive tool for the treatment of neglected diseases. The in vitro and in vivo efficacy of dichlorophen (DCP), an antiparasitic agent for intestinal parasites, and silica nanoparticles modified with DCP (NP-DCP) was evaluated against E. multilocularis larval stage. Both formulations showed a time and dose-dependent in vitro effect against protoscoleces. The NP-DCP had a greater in vitro efficacy than the drug alone or ABZ. In vivo studies demonstrated that the NP-DCP (4 mg kg-1) had similar efficacy to ABZ (25 mg kg-1) and greater activity than the free DCP. Therefore, the repurposing of DCP combined with silica nanoparticles could be an alternative for the treatment of echinococcosis.

Albendazole-lipid nanocapsules: Optimization, characterization and chemoprophylactic efficacy in mice infected with Echinococcus granulosus.

Cystic echinococcosis (CE), which is caused during the metacestode larval stage of Echinococcus granulosus, is a life-threatening disease and is very difficult to treat. At present, the FDA-approved antihelmintic drugs are mebendazole (MBZ), albendazole (ABZ) and its principal metabolite ABZ sulfoxide (ABZSO), but as these have a therapeutic efficacy over 50%, underlining the need for new drug delivery systems. The aim of this work was the optimization and characterization of previously developed ABZ lipid nanocapsules (ABZ-LNCs) and evaluate their efficacy in mice infected with E. granulosus. LNCs were prepared by the phase inversion technique and characterized in terms of size, surface charge, drug loading, and in vitro stability followed by an in vivo proof-of-concept using a murine model infected with E. granulosus. Stable particle dispersions with a narrow size distribution and high efficiency of encapsulation (≥90%) were obtained. ABZ-LNCs showed a greater chemoprophylactic efficacy than ABZ suspension administered by the oral route as 4 out of the 10 ABZ-LNCs treated mice did not develop any cysts, whereas the infection progressed in all mice from the ABZ suspension group. Regarding the ultrastructural studies of cysts, mice treated with ABZ-LNCs or ABZ suspension revealed changes in the germinal layer. However, the extent of the damage appeared to be greater after ABZ-LNC administration compared to the suspension treatment. These results suggest that ABZ-LNCs could be a promising novel candidate for ABZ delivery to treat CE.

Epidemiology, diagnosis, treatment and follow-up of cystic echinococcosis in asymptomatic carriers.

Background: Río Negro Province is endemic for cystic echinococcosis (CE). A CE control program includes early diagnosis in humans. During 1980-1996, screening was done with serology and surgery was the unique choice of treatment. Since 1997, ultrasound (US) has been the method of choice for screening, and new choices of treatment for asymptomatic carriers are discussed in the CE guidelines. Methods: Between 1997 and 2016, 42 734 abdominal USs were performed, 192 new asymptomatic cases were diagnosed and underwent a protocol according to the size, location and type of cyst. Treatment options included active surveillance (US monitoring, 83 [43.3%]), antiparasitic (albendazole, 92 [47.9%]) and surgery (17 [8.8%], including percutaneous treatment). Results: After 7.7 y of follow-up, of the cases under active surveillance, 28 (33.7%) had to change treatment: 5 (6%) to surgery and 22 (26.5%) to albendazole. Of the patients treated with albendazole, 3 (3.2%) were operated on and 13 (14%) were treated with a second cycle of albendazole. Conclusion: As a result of the present study, resolution of CE in a non-surgical way with albendazole is confirmed to be effective in asymptomatic carriers with CE1 or CE3a cysts. An update eliminates the strategy of active surveillance in type CE1 cysts <3 cm and is replaced by treatment with antiparasitic in all asymptomatic cases with CE1 or CE3a cysts <10 cm. The update also limits follow-up to 12-18 months to evaluate those cases with non-response to antiparasitic and switch to a surgical option.

Quiste hidatídico subcutáneo: reporte de dos casos en Huancayo, Perú / Subcutaneous hydatidic cyst: report of two cases in Huancayo, Peru

RESUMEN La hidatidosis es una infección zoonótica que puede invadir múltiples órganos en el ser humano. Sin embargo, el tejido subcutáneo es el órgano menos afectado por esta enfermedad, cuando esto ocurre se aprecia escasa sintomatología, lo que ocasiona periodos prolongados de enfermedad asociado a diagnóstico tardío y a una pobre respuesta a la terapia antiparasitaria. La sierra central del Perú es la zona con mayor prevalencia, presumiblemente por las inadecuadas medidas de saneamiento ambiental, la falta de educación y las casi inexistentes medidas de control de la enfermedad. Con el objetivo de discutir los problemas relacionados a la localización subcutánea y su probable fisiopatología, reportamos dos casos de hidatidosis subcutánea que se presentaron con lesiones tumorales de evolución prolongada y que no afectaron al hígado ni a los pulmones y que finalmente fueron tratados mediante extirpación quirúrgica debido a la falta de respuesta al tratamiento con albendazol.

ABSTRACT Hydatidosis is a zoonotic infection that can invade many organs in the human being. Nevertheless, the subcutaneous tissue is the less affected organ by this disease. When this disease appears, little symptomatology is observed, which causes prolonged periods of disease associated to delayed diagnosis and a poor answer to the antiparasitic therapy. The central mountain range of Peru is the geographical zone with the greatest prevalence, presumably due to the inadequate measures of environmental sanitation, the lack of education and the almost non-existent control measures of the disease. With the aim to discuss the problems related to the subcutaneous location and its probable physiopathology, this study reports two cases of subcutaneous hydatidosis that appeared with tumor lesions with a prolonged evolution and that did not affect the liver or the lungs and which were finally treated by means of surgical removal due to the lack of response to treatment with albendazol.

[Subcutaneous hydatidic cyst: report of two cases in Huancayo, Peru]. / Quiste hidatídico subcutáneo: reporte de dos casos en Huancayo, Perú.

Hydatidosis is a zoonotic infection that can invade many organs in the human being. Nevertheless, the subcutaneous tissue is the less affected organ by this disease. When this disease appears, little symptomatology is observed, which causes prolonged periods of disease associated to delayed diagnosis and a poor answer to the antiparasitic therapy. The central mountain range of Peru is the geographical zone with the greatest prevalence, presumably due to the inadequate measures of environmental sanitation, the lack of education and the almost non-existent control measures of the disease. With the aim to discuss the problems related to the subcutaneous location and its probable physiopathology, this study reports two cases of subcutaneous hydatidosis that appeared with tumor lesions with a prolonged evolution and that did not affect the liver or the lungs and which were finally treated by means of surgical removal due to the lack of response to treatment with albendazol.

La hidatidosis es una infección zoonótica que puede invadir múltiples órganos en el ser humano. Sin embargo, el tejido subcutáneo es el órgano menos afectado por esta enfermedad, cuando esto ocurre se aprecia escasa sintomatología, lo que ocasiona periodos prolongados de enfermedad asociado a diagnóstico tardío y a una pobre respuesta a la terapia antiparasitaria. La sierra central del Perú es la zona con mayor prevalencia, presumiblemente por las inadecuadas medidas de saneamiento ambiental, la falta de educación y las casi inexistentes medidas de control de la enfermedad. Con el objetivo de discutir los problemas relacionados a la localización subcutánea y su probable fisiopatología, reportamos dos casos de hidatidosis subcutánea que se presentaron con lesiones tumorales de evolución prolongada y que no afectaron al hígado ni a los pulmones y que finalmente fueron tratados mediante extirpación quirúrgica debido a la falta de respuesta al tratamiento con albendazol.

Anthelminthic activity of glibenclamide on secondary cystic echinococcosis in mice.

Cystic echinococcosis (CE) is a worldwide parasitic zoonosis caused by the larval stage of Echinococcus granulosus. Current chemotherapy against this disease is based on the administration of benzimidazoles (BZMs). However, BZM treatment has a low cure rate and causes several side effects. Therefore, new treatment options are needed. The antidiabetic drug glibenclamide (Glb) is a second-generation sulfonylurea receptor inhibitor that has been shown to be active against protozoan parasites. Hence, we assessed the in vitro and in vivo pharmacological effects of Glb against the larval stage of E. granulosus. The in vitro activity was concentration dependent on both protoscoleces and metacestodes. Moreover, Glb combined with the minimum effective concentration of albendazole sulfoxide (ABZSO) was demonstrated to have a greater effect on metacestodes in comparison with each drug alone. Likewise, there was a reduction in the cyst weight after oral administration of Glb to infected mice (5 mg/kg of body weight administered daily for a period of 8 weeks). However, in contrast to in vitro assays, no differences in effectiveness were found between Glb + albendazole (ABZ) combined treatment and Glb monotherapy. Our results also revealed mitochondrial membrane depolarization and an increase in intracellular Ca2+ levels in Glb-treated protoscoleces. In addition, the intracystic drug accumulation and our bioinformatic analysis using the available E. granulosus genome suggest the presence of genes encoding sulfonylurea transporters in the parasite. Our data clearly demonstrated an anti-echinococcal effect of Glb on E. granulosus larval stage. Further studies are needed in order to thoroughly investigate the mechanism involved in the therapeutic response of the parasite to this sulfonylurea.