- Repurposing of an old drug: In vitro and in vivo efficacies of buparvaquone against Echinococcus multilocularis. [Journal Article]
- IJInt J Parasitol Drugs Drug Resist 2018 Oct 31; 8(3):440-450
- The metacestode stage of the fox tapeworm Echinococcus multilocularis causes the lethal disease alveolar echinococcosis. Current chemotherapeutic treatment options are based on benzimidazoles (albend...
The metacestode stage of the fox tapeworm Echinococcus multilocularis causes the lethal disease alveolar echinococcosis. Current chemotherapeutic treatment options are based on benzimidazoles (albendazole and mebendazole), which are insufficient and hence alternative drugs are needed. In this study, we screened the 400 compounds of the Medicines for Malaria Venture (MMV) Pathogen Box against E. multilocularis metacestodes. For the screen, we employed the phosphoglucose isomerase (PGI) assay which assesses drug-induced damage on metacestodes, and identified ten new compounds with activity against the parasite. The anti-theilerial drug MMV689480 (buparvaquone) and MMV671636 (ELQ-400) were the most promising compounds, with an IC50 of 2.87 μM and 0.02 μM respectively against in vitro cultured E. multilocularis metacestodes. Both drugs suggested a therapeutic window based on their cytotoxicity against mammalian cells. Transmission electron microscopy revealed that treatment with buparvaquone impaired parasite mitochondria early on and additional tests showed that buparvaquone had a reduced activity under anaerobic conditions. Furthermore, we established a system to assess mitochondrial respiration in isolated E. multilocularis cells in real time using the Seahorse XFp Analyzer and demonstrated inhibition of the cytochrome bc1 complex by buparvaquone. Mice with secondary alveolar echinococcosis were treated with buparvaquone (100 mg/kg per dose, three doses per week, four weeks of treatment), but the drug failed to reduce the parasite burden in vivo. Future studies will reveal whether improved formulations of buparvaquone could increase its effectivity.
- Assessment of the global pattern of genetic diversity in Echinococcus multilocularis inferred by mitochondrial DNA sequences. [Review]
- VPVet Parasitol 2018 Oct 15; 262:30-41
- The aim of this review was to assess our current knowledge on phylogeography and global genetic structure of Echinococcus multilocularis populations originating from rodents, wild canid hosts, and hu...
The aim of this review was to assess our current knowledge on phylogeography and global genetic structure of Echinococcus multilocularis populations originating from rodents, wild canid hosts, and human. Six bibliographic databases were searched from 1990 to 2017, identifying a total of 110 publications. The cytochrome c oxidase subunit 1 (cox1) and cytochrome b (cytb) sequences of E. multilocularis from Asia, Europe, and North Americas were analyzed to estimate the diversity and neutrality indices, and genetic differentiation. A total of 69 (cox1, 36.7%) and 16 haplotypes (cytb, 19.2%) were grouped into various geographical clades. A parsimonious haplotype network demonstrated a star-like feature with haplo-groups Em2 (Asia: 36%), Em105 (Eastern Tibetan plateau: 4.8%), Em46 (Europe: 9.1%), Em73, (Europe: 2.7%) and Em92 (North Americas: 4.3%) as the most common haplotypes. A relatively high level of genetic diversity was detected in rodent-derived E. multilocularis isolates (Haplotype diversity: 0.944), wild canids (Hd: 0.912), and human origin (Hd: 0.704). The highest number of haplotypes (n = 59) and the highest haplotype diversity (0.969) were identified in the Asian and European populations, respectively. Cladistic phylogenetic tree indicated the European clade has a sister relationship with the Asian clade. However, some North American haplotypes were assigned to the European clade together with haplotypes from Poland. The statistically significant Fst values indicated that E. multilocularis populations of Asian-European, Asian-North American, and European-North American origins were genetically differentiated (Fst: 0.22624 to 0.43059). An occurrence of distinct parasite populations suggests that E. multilocularis derived from glacial refugia have been plausibly sustained by indigenous hosts during the Pleistocene Epoch.
- Alveolar Echinococcosis Mimicking a Hepatic Neoplasm with Lymph Node Metastasis: A Case Report. [Journal Article]
- CRCase Rep Gastroenterol 2018 Sep-Dec; 12(3):587-596
- A 37-year-old man had an asymptomatic 17-mm mass in the liver by health check with ultrasonography. Five years later, he was referred to our hospital because the mass was slightly enlarged with a per...
A 37-year-old man had an asymptomatic 17-mm mass in the liver by health check with ultrasonography. Five years later, he was referred to our hospital because the mass was slightly enlarged with a peripancreatic lymph node. We performed endoscopic ultrasonography fine-needle aspiration (EUS-FNA) to evaluate a lymph node, but it showed amorphous eosinophilic material and eosinophilic infiltrate in necrotic tissue of toothpaste-like white specimen. However, we diagnosed as potentially malignant liver mass with lymph node metastasis because of 2-deoxy-2-(fluorine-18) fluorodeoxyglucose uptake. We then performed hepatectomy and enucleation of the pancreas. DNA polymerase chain reaction analysis revealed Echinococcus multilocularis infection. Retrospectively, we could find a part of Echinococcus in the specimens of EUS-FNA.
- Remnant Liver-to-Standard Liver Volume Ratio Below 40% is Safe in Ex Vivo Liver Resection and Autotransplantation. [Journal Article]
- JGJ Gastrointest Surg 2018 Oct 29
- CONCLUSIONS: Patients with a smaller RLV/SLV did not have outcomes inferior to those with a larger RLV/SLV. Further studies are warranted to clarify the factors that contribute to preoperative volumetric estimation and the safe lower limits for ERAT.
- A Case of Echinococcal Cyst of the Lung. [Journal Article]
- RMRespir Med Case Rep 2018; 25:286-292
- Echinococcosis, also known as Hydatid disease, is caused by the larvae of the tapeworm Echinococcus. It is globally prevalent and is a major clinical health concern. It is endemic in most underdevelo...
Echinococcosis, also known as Hydatid disease, is caused by the larvae of the tapeworm Echinococcus. It is globally prevalent and is a major clinical health concern. It is endemic in most underdeveloped regions including Asia, the Mediterranean, South America and Africa. There are four species within the genus Echinococcus, with E. granulosus and E. multilocularis being the most common, causing Cystic Echinococcosis (CE) and Alveolar Echinococcosis (AE). The clinical presentation of the disease is non-specific. It commonly involves the liver, lungs, brain and adrenal glands. Pulmonary disease is significant for its propensity to affect children and young adults. This young population accounts for ∼50% of pulmonary hydatid cysts . Cysts are known to grow extensively in size. Many patients are asymptomatic and have only a solitary cyst. Symptoms arise from enlargement of the cyst and from eroding and pressure applied by the cyst to blood vessels and organs. If rupture of the cyst occurs it can lead to immunologic reactions such as asthma and anaphylaxis. Echinococcus in the lung can pose diagnostic dilemmas, as their homogeneous density and tendency to occur alone may cause them to be confused with squamous cell carcinoma, adenocarcinoma, solitary metastasis, and abscess . Our case is of such a patient who was found to have a 6 cm mass in the right middle lobe (RML) found on a chest X-ray during evaluation of back pain. Echinococcus should always be included in a differential diagnosis of any mass lesions especially in immigrant populations from endemic countries.
- The use of contrast-enhanced ultrasound (CEUS) for the diagnostic evaluation of hepatic echinococcosis. [Journal Article]
- CHClin Hemorheol Microcirc 2018 Oct 15
- CONCLUSIONS: CEUS depicts a safe method for the evaluation of echinococcal liver disease. In addition to serological tests and grey scale ultrasound, CEUS imaging could be integrated as an easily accessible tool helping to describe hypervascularization as a sonomorphological correlate for active perilesional inflammation of echinococcal manifestations. CEUS may further help to differentiate between CE and AE and also to evaluate treatment outcome.
- Immunotherapy of alveolar echinococcosis via PD-1/PD-L1 immune checkpoint blockade in mice. [Journal Article]
- PIParasite Immunol 2018 Oct 13; :e12596
- The growth potential of the tumour-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly dependent upon the nature/function of the periparasitic adaptive host...
The growth potential of the tumour-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly dependent upon the nature/function of the periparasitic adaptive host immune-mediated processes. PD-1/PD-L1 pathway (programmed cell death 1), which inhibits lymphocytic proliferation in tumour development, is over-expressed at the chronic stage of AE. We tested the impact of a PD-1/PD-L1 pathway blockade on the outcome of both chronic AE (intraperitoneal metacestode inoculation, secondary AE and SAE) and acute AE (peroral egg infection, primary AE and PAE). To assess the parasite proliferation potential, we measured parasite mass weight for SAE and liver lesion number for PAE. In both models, the parasite load was significantly decreased in response to anti-PD-L1 antibody treatment. In SAE, anti-PDL1 administration was associated with increased Th1 response parameters and decreased Treg responses, while in PAE anti-PDL1 administration was associated with fewer lesions in the liver and decreased Treg/Th2 responses. Our findings highly suggested that a PD-1/PD-L1 pathway blockade triggered the host immune responses in favour of an immune-mediated control of E. multilocularis proliferation. Based on this, future studies that combine PD-1/PD-L1 blockade with a parasitostatic albendazole medication may yield in a putatively curative therapeutic approach to control alveolar echinococcosis.
- Disseminated cerebral hydatid disease (multiple intracranial echinococcosis). [Journal Article]
- PNPract Neurol 2018 Oct 10
- Intracranial echinococcosis is relatively uncommon and usually occurs in the context of echinococcal lesions elsewhere in the body, mostly liver and lung. Multiple intracranial lesions can result fro...
Intracranial echinococcosis is relatively uncommon and usually occurs in the context of echinococcal lesions elsewhere in the body, mostly liver and lung. Multiple intracranial lesions can result from rupture of an initial single intracranial cyst (in cystic echinococcosis) or from dissemination of systemic disease of the lung, liver or heart (cystic and alveolar echinococcosis). The two main subtypes, cystic and alveolar echinococcosis, present differently and have distinct imaging features in the brain. We discuss the presentation, imaging findings and clinical course of three cases (two cystic and one alveolar) of intracranial echinococcal disease in adults.
- Biological characteristics of 18F-FDG PET/CT imaging of cerebral alveolar echinococcosis. [Journal Article]
- MMedicine (Baltimore) 2018; 97(39):e11801
- This study aims to analyze the characteristics of F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) for cerebral alveolar echinococcosis (CAE).Twenty-five CAE patie...
This study aims to analyze the characteristics of F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET/CT) for cerebral alveolar echinococcosis (CAE).Twenty-five CAE patients underwent F-FDG PET/CT, and the diagnosis was confirmed by clinical and surgical pathology. The F-FDG PET/CT results were subject to visual and semiquantitative analysis, and the difference in F-FDG SUVmax for lesions among the 3 types of CAE was evaluated.In the 25 CAE patients, 62 lesions were detected by F-FDG PET/CT, and these lesions were classified into 3 types, according to the characteristics of the lesion's uptake of F-FDG on PET images: type I, 17 lesions, FDG was concentrated into a mass radioactive distribution in the CAE foci; type II, 28 lesions, FDG presented a annular concentrated radioactive distribution around the CAE foci; type III, 17 lesions, FDG in the CAE foci presented a radioactive distribution with defects and sparse areas. The difference in F-FDG SUVmax between type I and type II CAE was not statistically significant (P > .05), the difference in F-FDG SUVmax between type I and type III CAE was statistically significant (P < .001), and the difference in F-FDG SUVmax between type II and type III CAE was statistically significant (P < .001);The F-FDG PET manifestations of CAE are classified into 3 types. Both type I and type II may have invasive activity, while the lesions of type III CAE show that the focus is relatively stable or at a stationary phase. If there are no definite alveolar echinococcus focus in other sites, these patients can temporarily delay the treatment. It is recommended that the patient should undergo whole body PET/CT once a year to dynamically observe the bioactivity and size of type III CAE lesions and assess the presence of new echinococcus lesions in the rest of the body.
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- Molecular characterization of human echinococcosis in Sichuan, Western China. [Journal Article]
- ATActa Trop 2018 Sep 29; 190:45-51
- Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are highly co-endemic in Sichuan, a part of Qinghai-Tibet Plateau where is a typical Tibetan nomadic community living area. In order to bet...
Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are highly co-endemic in Sichuan, a part of Qinghai-Tibet Plateau where is a typical Tibetan nomadic community living area. In order to better understand the Echinococcus spp. of human being infected origins in this area, 140 lesions were collected from echinococcosis patients who were received operations during the period of 2014-2016 in different geographic districts in this region. Partial DNA sequences of the mitochondrial cox1 gene were analyzed. The genetic characterization of the isolates from 3 different places including Ganzi, Aba and Liangshan were assessed. Of all the 140 samples, the great majority was identified as Echinococcus granulosus sensu stricto (n = 108). Echinococcus multilocularis was confirmed to be another important pathogen of the human infections (n = 31). Additionally, one Echinococcus canadensis (G6/7) isolate from Ganzi was confirmed. Comparing the clinical diagnosis with the sequencing results, 6.4% (9/140) of the cases were misdiagnosed between AE and CE, and another 8.6% (12/140) were unclassified to sub-type in echinococcosis. Higher rates of misdiagnosis and unclassified diagnosis were found in AE cases (12.9%, 4/31 and 16.1%, 5/31 respectively) compared to CE (4.6%, 5/109 and 6.4%, 7/109 respectively). In E.granulosus s.s., a total of 34 haplotypes were detected, and 4 haplotypes were inferred from E.multilocularis. The haplotype networks of the 2 species exhibited a similar star-shaped feature with a dominant haplotype in the center. Geographically specific haplotypes were observed in Ganzi and Aba respectively. This study provides insight into the current species causing human echinococcosis in the Tibetan districts of Sichuan. E.granulosus s.s. and E.multilocularis are confirmed to be the main causative agents, and the existence of E.canadensis (G6/7) is also observed in the region. Molecular diagnosis was proven to be essential for the confirmation of human echinococcosis in the area.