Search Results (49)

Background/Objectives: Alveolar echinococcosis (AE), caused by Echinococcus multilocularis larvae, poses a significant global health concern. Primarily affecting regions in the northern hemisphere, such as northwest China, which are vital for animal husbandry, it often results in severe hepatic impairment in the host. However, there remains a dearth of knowledge concerning changes in gene expression profiles during the progression of AE. In this study, we employed transcriptome sequencing (RNA sequencing, RNA-Seq) to detect alterations in gene expression profiles in the liver tissues of mice with AE. Our aims were to understand the transcriptome differences in the liver during E. multilocularis infection and to explore the molecular mechanisms underlying the early progression of this disease. Methods: We established a mouse model of AE by intraperitoneally injecting protoscoleces of E. multilocularis. All the inoculated mice were randomly divided into four groups. Liver tissues were collected at 6, 12, 19, and 25 weeks after inoculation. Paired non-infected mouse-derived liver tissues were used as controls, and transcriptome sequencing was carried out. Results: A total of 629 differentially expressed genes (DEGs) were identified. Among them, 370 genes were upregulated and 259 genes were downregulated. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these DEGs were significantly associated with immune system modulation, the cell cycle, and the fibrosis process during the pathological changes. Additionally, weighted gene co-expression network analysis (WGCNA) identified several genes, including CCNA2, BIRC5, KIF2C, OTC, TLR2, and NCKAP1L. These hub genes involved in immunoinflammatory processes may be related to E. multilocularis larvae infection. Conclusions: The findings of this research provide a theoretical foundation for a more in-depth understanding of the molecular mechanisms of AE. They offer valuable insights into the molecular mechanisms and potential key factors involved in the pathogenesis of this disease. Full article

Alveolar echinococcosis (AE), caused by Echinococcus multilocularis (E. multilocularis), is a severe parasitic zoonosis that is potentially fatal for humans. The parasite is primarily transmitted by wildlife, with red foxes acting as definitive hosts and rodents as intermediate hosts, while humans can become accidental but dead-end hosts. The aim of this study is to use EmsB typing on E. multilocularis isolates from human AE cases and local animals such as foxes and rodents. In this study, retrospective EmsB typing was performed on 39 samples, including 11 tissue samples from 10 patients, 18 fecal swabs from foxes, and 10 tissue samples from rodents. A dendrogram was created to determine the EmsB profiles present. The results showed that all the rodent samples were associated with the EmsB P1 profile (10/10), while the human and fox samples shared the EmsB profile P1 (5/11 humans and 8/18 foxes), a profile near P4 (2/11 humans and 3 foxes), and a profile near P8 (1/11 humans and 1/18 foxes). The study demonstrates that the same EmsB profiles circulate among humans and animals, confirming that wildlife reservoirs play a key role in transmission. Full article

Alveolar echinococcosis (AE) is a chronic and potentially fatal zoonotic parasitic disease that seriously affects the host’s health. It is caused by the proliferation of Echinococcus multilocularis larvae within the liver. Due to its long incubation period following host infection, early diagnosis of the disease is currently not feasible. Treatment options are extremely limited, with the only choice being curative surgical resection combined with benzimidazole medication. Thus, the development of early, rapid, and minimally invasive diagnostic methods is crucial for enhancing patient prognosis. This study conducted proteomic and metabolomic analyses of protein and metabolite changes in the serum of a treatment group and control group, aiming to compare the differences between them. Overall, 22 proteins showed significant differences between the treatment and control groups, primarily involved in carbohydrate metabolism, lipid metabolism, and amino acid metabolism. The upregulation of genes related to immune response and enhanced glycolysis were observed, possibly associated with the reproduction of E. multilocularis in the liver. A total of 182 metabolites were screened to distinguish between the treatment group and control group. A significant increase in the cytochrome P450 (cP450) metabolite of arachidonic acid indicated signs of renal and splenic involvement in the treatment group. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted a strong association between amino acid metabolism and the development of AE. The observed changes in amino acid levels may provide nutrients that facilitate E. multilocularis colonization and contribute to the pathogenesis of AE. In summary, by investigating the different characteristics of the AE and control group through proteomic (n = 4/group/time point) and metabolomic (n = 8/group/time point) analyses, potential serum biomarkers for diagnosing mice with AE were identified. Full article

In the present work, we describe the clinical–pathological case of an 11-month-old Border Collie dog, which was presented by its owner to a private veterinary clinic for the purpose of determining the diagnosis and subsequent therapy. The owner reports anamnestic data of abdominal enlargement, persistent apathy, fatigue, and vomiting. A complete examination of the patient was performed, consisting of clinical, hematological, and biochemical blood tests, X-ray, and USG examinations. Based on the findings, a probatory laparotomy was indicated, during which a large multi-lobular cystic irregular mass was detected, affecting the entire liver parenchyma, including macroscopic metastatic foci of the omentum and diaphragm. Due to the inoperable finding, the patient was humanely euthanized during the surgical procedure. Subsequently, an autopsy was performed with the collection of samples for histopathological and PCR examination of the tissue. Serological examination was also performed. The results confirmed a rare generalized form of alveococcosis (Echinococcus multilocularis) in the dog as an intermediate host. Full article

Alveolar Echinococcosis (AE) is a serious zoonotic disease caused by infection of Echinococcus multilocularis larvae. To survive within the host, E. multilocularis has developed a complex immune evasion mechanism including the inhibition of complement activation. This study focused on a calreticulin secreted by E. multilocularis (EmCRT) and its role in binding ability to human MBL and inhibiting MBL-mannose-mediated lectin pathway of complement activation. Results demonstrated the binding of recombinant EmCRT protein to both external and natural MBL in serum and the subsequent inhibition of MBL-mannose-initiated lectin pathway reflected by the reduced formation of complement intermediate products C3b and C4b. Fragment mapping determined that the MBL binding site was located within the S-domain of EmCRT. Combining with its role in inhibiting C1q-initiated classical complement activation in our previous study, the inhibition of MBL-mannose-initiated lectin pathway identified in this study suggests EmCRT plays an important role in the immune evasion of E. multilocularis alveolar larvae against host complement attack as a survival strategy within human tissue. This study supports the approach of using EmCRT as a good candidate for vaccine and drug development against E. multilocularis infection. Full article

The tapeworms Echinococcus granulosus and Echinococcus multilocularis cause two different clinical manifestations in humans: cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. Both forms of echinococcosis manifest primarily in the liver, while other organs or tissues are less frequently affected. Simultaneous occurrence of CE and AE is extremely rare, and all previously reported patients exhibited affected livers, while simultaneous infection without liver involvement has not yet been described. Herein, we present an exclusively extrahepatic E. granulosus and E. multilocularis coinfection localized between the calf muscles of a patient. Due to progressive painful local swelling, an abscess was suspected, but there was no improvement after the administration of multiple courses of antibiotics. When imaging diagnostics suggested a parasitic origin of the two identified cystic lesions, positive serology for both species indicated a dual infection. Albendazole therapy was started, and extensive surgical excision was performed. Both species were confirmed using PCR and sequencing from intraoperative samples. The current case shows that coinfection without liver involvement can occur, even in patients from low-incidence regions, which should be considered in the differential diagnosis of patients with unusual clinical presentation. Full article

Metacestodes of Echinococcus multilocularis are the causative agents of alveolar echinococcosis, a neglected, life-threatening, zoonotic disease. To study these metacestodes in vitro, a model system using a culture medium conditioned by rat hepatoma cells is available. A key question is how the parasite interacts with the host and, in particular, which host-derived compounds are taken up. In this study, we focus on the uptake of host-derived proteins. Studies with artificially labeled proteins suggest that this uptake may occur independently of protein size or charge. Closer investigation using proteomics draws, however, a different picture. Of 1170 host (i.e., rat or bovine) proteins as identified by LC-MS/MS-based proteomics present in the culture medium, only 225 are found in metacestode vesicle tissue or fluid. Moreover, their relative abundances differ. Serum albumin, the most abundant culture medium host protein, is only the third most abundant protein in vesicle fluid, where Alpha-2-HS-glycoprotein becomes the most abundant protein. In vesicle fluid obtained ex vivo from experimentally infected mice, the situation is again different, with histone isoforms as the most abundant proteins. This suggests that while maintaining their internal milieu constant, metacestodes may adjust the spectrum of host proteins taken up. Potential uptake mechanisms and functions are discussed. Full article

Alveolar echinococcosis (AE) in humans is caused by the larval (metacestode) stage of Echinococcus multilocularis, commonly known as the ‘fox tapeworm’. This disease predominantly targets the liver and has an invasive growth pattern, allowing it to spread to adjacent and distant tissues. Due to its gradual progression and tumour-like characteristics, early diagnosis and prompt intervention are crucial, particularly as there are currently no highly effective vaccines or chemotherapeutics against AE. Current estimates suggest that ~10,500 new infections occur annually worldwide; however, more research is required to refine the prevalence and incidence data for both human and animal hosts in endemic areas of the world. This article discusses the biology of E. multilocularis, outlines aspects of the pathogenesis, diagnosis, treatment, and management of AE, reviews its global distribution, annual incidence, and prevalence, highlights the role of molecular parasitology in advancing therapeutic strategies, and presents recommendations for improving the prevention and control of AE in human populations. Full article

Alveolar echinococcosis (AE), caused by the larval stage of the tapeworm Echinococcus multilocularis, is a serious parasitic disease that presents significant health risks and challenges for both patients and healthcare systems. Accurate and timely diagnosis is essential for effective management and improved patient outcomes. This review summarizes the latest diagnostic methods for AE, focusing on serological tests and imaging techniques such as ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT). Each imaging modality has its strengths and limitations in detecting and characterizing AE lesions, such as their location, size, and invasiveness. US is often the first-line method due to its non-invasiveness and cost-effectiveness, but it may have limitations in assessing complex lesions. CT provides detailed anatomical information and is particularly useful for assessing bone involvement and calcification. MRI, with its excellent soft tissue contrast, is superior for delineating the extent of AE lesions and their relationship to adjacent structures. PET/CT combines functional and morphological imaging to provide insights into the metabolic activity of lesions, which is valuable for monitoring treatment response and detecting recurrence. Overall, this review emphasizes the importance of a multifaceted diagnostic approach that combines serological and imaging techniques for accurate and early AE diagnosis, which is crucial for effective management and improved patient outcomes. Full article

Echinococcosis, one of the most serious and life-threatening parasitic forms of zoonosis worldwide, is caused by the larvae of Echinococcus granulosus (E. granulosus) and Echinococcus multilocularis (E. multilocularis). Various drugs are being applied clinically to treat zoonosis; however, their therapeutic efficacy remains a great challenge, especially with albendazole as the preferred drug of choice. Receptor tyrosine kinase (RTK) signaling controls normal cellular proliferation, differentiation, and metabolism in humans and mammals, which are intermediate hosts of E. granulosus and E. multilocularis. Disruption of RTK signaling can cause various forms of carcinogenesis and exacerbate the progression of certain forms of parasitic disease. As a result, a significant number of studies on tyrosine kinase inhibitors (TKIs) have been conducted for the treatment of cancer and parasitic infection, with some TKIs already approved for clinical use for cancer. Notably, RTK signaling has been identified in the parasites E. granulosus and E. multilocularis; however, the mechanisms of RTK signaling response in Echinococcus–host intercommunication are not fully understood. Thus, understanding the RTK signaling response in Echinococcus–host intercommunication and the potential effect of RTK signaling is crucial for identifying new drug targets for echinococcosis. The present review illustrates that RTK signaling in the host is over-activated following infection by E. granulosus or E. multilocularis and can further facilitate the development of metacestodes in vitro. In addition, some TKIs exert strong parasitostatic effects on E. granulosus or E. multilocularis, both in vitro and/or in vivo, through downregulation of RTK signaling molecules. The summarized findings suggest that RTK signaling may be a promising drug target and that TKIs could be potential anti-Echinococcus drugs warranting further research. Full article

We aimed to investigate the species composition of a small mammal community and the prevalence of Echinococcus spp. in a typical endemic area of the Tibetan Plateau. One pika and five rodent species were identified based on the morphological characteristics of 1278 small mammal specimens collected during 2014–2019. Detection of Echinococcus DNA in tissue samples from small mammal specimens revealed that Ochotona curzoniae (pika, total prevalence: 6.02%, 26/432), Neodon fuscus (5.91%, 38/643), N. leucurus (2.50%, 3/120), and Alexandromys limnophilus (21.74%, 10/46) were infected by both E. multilocularis and E. shiquicus; Cricetulus longicaudatus (16.67%, 1/6) was infected by E. shiquicus; and no infection was detected in N. irene (0/15). Neodon fuscus and O. curzoniae were the two most abundant small mammal species. There was no significant difference in the prevalence of pika and the overall rodent species assemblage (6.26%, 53/846); however, the larger rodent populations suggested that more attention should be paid to their role in the transmission of echinococcosis in the wildlife reservoir, which has long been underestimated. Moreover, although DNA barcoding provides a more efficient method than traditional morphological methods for identifying large numbers of small mammal samples, commonly used barcodes failed to distinguish the three Neodon species in this study. The close genetic relationships between these species suggest the need to develop more powerful molecular taxonomic tools. Full article

A prospective study on 110 patients with echinococcosis at Dr. Khuroo’s Medical Clinic, Srinagar, Kashmir, India, from March 2019 to April 2024 identified 12 cases (4 males, 8 females; mean age of 46.58 ± 11.97 years) of Alveolar echinococcosis (AE). Two patients were detected through ultrasound examinations carried out for unrelated causes; one presented with features of liver abscess, and nine had pain in the right upper quadrant for a mean period of 2.2 ± 1.79 years. All had the liver as the primary organ involved, with 15 tumor masses of a mean maximum diameter of 9.22 ± 3.21 cm and volume of 426 ± 374.61 cm³. Tumors placed centrally had invaded vessels and the biliary tract in eight patients, and those placed peripherally had invaded the liver capsule and adjacent organs in nine patients. Histologic examination of liver biopsies or resected organs revealed necrotic lesions, calcifications, and granulomatous inflammation with slender, thin-walled vesicles of bizarre configuration that stained strongly eosinophilic with periodic acid Schiff. Two patients had segmental liver resections; one was treated with liver aspiration, while the other nine with advanced disease received chemotherapy with albendazole along with praziquantel. Patients showed clinical improvement on a median follow-up of 12 months (range 1 to 60 months); however, MRI T2-weighted images and ¹⁸F-FDG-PET-CECT scans in two patients showed active disease on follow-up at one and five years, respectively. A systematic review detected 146 cases of AE in India from 1980 to April 2024. Twenty cases were from foreign countries, mostly from Central Asian republics, and 118 (93.65%) of the remaining 126 Indian patients were permanent residents of Kashmir Valley. The disease affected a population of 79,197 residing in 22 villages from 5 border districts of the valley. These villages were either high in or adjacent to the Himalayan mountain range. Disease prevalence in the affected population was 146.47/10⁵ (males 131.53/10⁵ and females 163.18/10⁵) and the incidence was 12.41/10⁵/year (males 11.16/10⁵/year and females 13.81/10⁵/year). Possible causes of the emergence of AE are discussed, and future directions for research to face this challenge arebeen identified. Full article

Echinococcosis poses a significant concern in the fields of public health and veterinary care as it can be transmitted between animals and humans. The primary endemic subtypes are cystic echinococcosis (CE) and alveolar echinococcosis (AE), which result from infestation by Echinococcus granulosus and Echinococcus multilocularis, respectively. A prominent epidemic of echinococcosis greatly affects the Tibet Autonomous Region (TAR) in China. A new technique called the loop-mediated isothermal amplification–lateral flow dipstick (LAMP-LFD) test is introduced in this research to differentiate between E. granulosus and E. multilocularis using their repetitive genetic sequences. The test is characterized by its portable nature, simple operation, quick result production, high sensitivity, and low susceptibility to aerosol contamination. The LAMP-LFD method demonstrated an exceptional minimal detection limit, reaching levels as low as approximately 1 fg/μL (femtogram per microliter) of genomic DNA. The assay’s specificity was assessed, and no cross-reactivity was seen. A total of 982 dog fecal samples were collected from 54 counties in the TAR region between July 2021 and June 2022. The established method underwent validation using a commercially available ELISA kit. The agreement rate between the LAMP-LFD and ELISA methods was 97.25%, with a sensitivity of 96.05% and a specificity of 97.35%. The assay described in this study improves specificity by using a double-labeled probe, and it reduces the risk of false-positive results caused by aerosol contamination through the use of a sealed device. This makes it a suitable choice for quickly and accurately identifying the two main types of Echinococcus in field settings. Full article

Alveolar echinococcosis (AE) stands as a perilous zoonotic affliction caused by the larvae of Echinococcus multilocularis. There is an imperative need to explore novel therapeutic agents or lead compounds for the treatment of AE. Asparagusic acid, characterized by its low toxicity and possessing antimicrobial, antioxidant, and anti-parasitic attributes, emerges as a promising candidate. The aim of this study was to investigate the in vivo and in vitro efficacy of asparagusic acid against E. multilocularis. Morphological observations, scanning electron microscopy, ROS assays, mitochondrial membrane potential assays, and Western blot were used to evaluate the in vitro effects of asparagusic acid on protoscoleces. The effects of asparagusic acid on vesicles were assessed via PGI release, γ-GGT release, and transmission electron microscopy observations. CellTiter-Glo assays, Caspase3 activity assays, flow cytometry, and Western blot were used for an evaluation of the effect of asparaginic acid on the proliferation and apoptosis of germinal cells. The in vivo efficacy of asparagusic acid was evaluated in a murine AE model. Asparagusic acid exhibited a pronounced killing effect on the protoscoleces post-treatment. Following an intervention with asparagusic acid, there was an increase in ROS levels and a decline in mitochondrial membrane potential in the protoscolex. Moreover, asparagusic acid treatment resulted in the upregulation of PGI and γ-GGT release in metacestode vesicles, concomitant with the inhibition of germinal cell viability. Furthermore, asparagusic acid led to an enhanced relative expression of Caspase3 in the culture supernatant of both the protoscoleces and germinal cells, accompanied by an increase in the proportion of apoptotic germinal cells. Notably, asparagusic acid induced an augmentation in Bax and Caspase3 protein expression while reducing Bcl2 protein expression in both the protoscoleces and germinal cells. In vitro cytotoxicity assessments demonstrated the low toxicity of asparagusic acid towards normal human hepatocytes and HFF cells. Additionally, in vivo experiments revealed that asparagusic acid administration at doses of 10 mg/kg and 40 mg/kg significantly reduced metacestode wet weight. A histopathological analysis displayed the disruption of the germinal layer structure within lesions post-asparagusic acid treatment, alongside the preservation of laminated layer structures. Transmission electron microscopy further revealed mitochondrial swelling and heightened cell necrosis subsequent to the asparagusic acid treatment. Furthermore, asparagusic acid promoted Caspase3 and Bax protein expression while decreasing Bcl2 protein expression in perilesional tissues. Subsequently, it inhibited the expression of Ki67, MMP2, and MMP9 proteins in the perilesional tissues and curbed the activation of the PI3K/Akt signaling pathway within the lesion-host microenvironmental tissues. Asparagusic acid demonstrated a pronounced killing effect on E. multilocularis, suggesting its potential as a promising therapeutic agent for the management of AE. Full article

The cestode Echinococcus multilocularis, which mainly dwells in the liver, leads to a serious parasitic liver disease called alveolar echinococcosis (AE). Despite the increased attention drawn to the immunosuppressive microenvironment formed by hepatic AE tissue, the immunological characteristics of hepatic dendritic cells (DCs) in the AE liver microenvironment have not been fully elucidated. Here, we profiled the immunophenotypic characteristics of hepatic DC subsets in both clinical AE patients and a mouse model. Single-cell RNA sequencing (scRNA-Seq) analysis of four AE patient specimens revealed that greater DC numbers were present within perilesional liver tissues and that the distributions of cDC and pDC subsets in the liver and periphery were different. cDCs highly expressed the costimulatory molecule CD86, the immune checkpoint molecule CD244, LAG3, CTLA4, and the checkpoint ligand CD48, while pDCs expressed these genes at low frequencies. Flow cytometric analysis of hepatic DC subsets in an E. multilocularis infection mouse model demonstrated that the number of cDCs significantly increased after parasite infection, and a tolerogenic phenotype characterized by a decrease in CD40 and CD80 expression levels was observed at an early stage, whereas an activated phenotype characterized by an increase in CD86 expression levels was observed at a late stage. Moreover, the expression profiles of major immune checkpoint molecules (CD244 and LAG3) and ligands (CD48) on hepatic DC subsets in a mouse model exhibited the same pattern as those in AE patients. Notably, the cDC and pDC subsets in the E. multilocularis infection group exhibited higher expression levels of PD-L1 and CD155 than those in the control group, suggesting the potential of these subsets to impair T cell function. These findings may provide valuable information for investigating the role of hepatic DC subsets in the AE microenvironment and guiding DC targeting treatments for AE. Full article