Search Results (73)

Alveolar echinococcosis (AE) is a zoonotic disease caused by the larval form of the tapeworm Echinococcus multilocularis, which is considered one of the most dangerous parasites for humans. E. multilocularis infections are most frequently observed in forestry workers, farmers, hunters, berry harvesters, and workers employed in animal shelters. The subject of this study was a four-year follow-up profile of cytokines, including tumor necrosis factor alpha (TNFα), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-4 (IL-4), and interleukin-10 (IL-10), in a patient with advanced liver alveolar echinococcosis and non-optimal antiparasitic treatment. Ultrasound, computed tomography (CT) of the abdomen, X-ray, CT of the chest, and magnetic resonance imaging (MRI) of the head were performed during the observation and treatment of the AE patient. After antiparasitic treatment was initiated, decreased activity of the gamma-glutamyl transpeptidase (GGTP), decreased serum concentrations of immunoglobulin E, C-reactive protein (CRP), and the pro-inflammatory cytokines TNFα, IL-1, and IL-6 were observed, as well as slightly increased levels of the anti-inflammatory cytokines (IL-4 and IL-10). Conclusions. During a four-year follow-up in a patient with advanced hepatic alveolar echinococcosis and non-optimal antiparasitic treatment, a decrease in proinflammatory cytokines (TNFα, IL-1β, IL-6) and a slight increase in anti-inflammatory cytokines (IL-4, IL-10) were detected. A better understanding of cytokine regulation in infectious diseases may be important to the development of new therapeutic strategies aimed at antiparasitic treatment. We suggest that broad initiatives (preferably at the local community level) should be implemented to raise awareness of the threat of alveolar echinococcosis and methods for avoiding E. multilocularis infection. Full article

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

Estimating the human impact on parasites in wildlife is essential to create efficient strategies to control diseases and improve public health. This study assessed the human influence on the parasite burden of the two commonest canine mesocarnivores, the red fox (N = 194) and the golden jackal (N = 151), in Europe. We compared the infracommunity crowding index, parasite diversity, prevalence, and abundance of different parasite taxa, and the presence of Echinococcus multilocularis between groups of hosts, such as jackals and foxes hunted at different distances from human settlements. The analysis of hosts’ distribution ascertained that 61.2% of the investigated wild canids were hunted in a 500–1750 m ring around the human settlements. Ancylostomatidae proved the most prevalent taxon (>60%), while Echinococcus multilocularis and Dipylidium caninum occurred least frequently. The two taxa that mostly contributed to the crowding of infracommunities were Ancylostomatidae and Toxocaridae, with a negative correlation between their abundances (Spearman’s ρ = −0.445, p < 0.001). Parasite infracommunities were more crowded in Echinococcus multilocularis infected foxes (p = 0.02) and jackals (p = 0.001). Our study highlighted that human modification of landscapes worsened the parasite burden of wild mesocarnivores, which could increase the public health risk of zoonotic parasites. 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

Berries represent healthy dietary options and contain bioactive compounds associated with a decreased risk of diseases. Despite representing healthy food choices, these products can be contaminated by pathogenic microorganisms, including parasites. Among foodborne parasites, Giardia duodenalis, Cryptosporidium parvum, Cyclospora cayetanensis, Toxoplasma gondii, and Echinococcus multilocularis are of significant public health importance and have been recently detected in fresh berries in Europe, including Italy. Berries can be purchased fresh or frozen, and it is worrying that even frozen berries could represent a risk for the consumer. In fact, several parasites can resist freezing temperatures and have been responsible for outbreaks of infection. The aim of this study was to investigate the presence of G. duodenalis, C. parvum, C. cayetanensis, T. gondii, and E. multilocularis in frozen berries with simplex and multiplex real-time PCR protocols. A total of 108 packages of mixed frozen berries were bought from supermarkets located in a south-eastern region of Italy. The samples were tested using two simplex real-time PCR protocols targeting C. parvum and G. duodenalis, respectively, and a multiplex real-time PCR targeting C. cayetanensis, T. gondii, and E. multilocularis. None of the investigated parasites were detected in the frozen berry samples tested. This research topic is still unexplored and of great current interest. These results represent a first attempt to investigate parasitic contamination of frozen berries sold on the Italian market, but further large-scale surveys are required. Full article

Introduction: Alveolar echinococcosis is one of the most pathogenic zoonoses caused by the larval forms of Echinococcus multilocularis. It is endemic in central Europe, but from 2001 to 2018, eight European countries reported their first cases of alveolar echinococcosis. These numbers testify to unprecedented spread of the infection. Case report: We report the first case of alveolar echinococcosis from southern Croatia that was incidentally found in an immunocompromised 70-year-old male patient. He was admitted to the hospital due to macrohematuria and renal insufficiency. Diagnostic assessment of kidney impairment revealed a large liver infiltration whose radiographic appearance was suspicious of a cancer. Nevertheless, histopathological and molecular analysis of the liver biopsy confirmed alveolar echinococcosis. The lesion was irresectable due to expansion along the major liver vessels. Therefore, conservative treatment with albendazole was started and the existing immunosuppressive therapy was modulated. The control imaging following 11 months of albendazole treatment showed regression of the lesions. Conclusions: It is not clear whether this case was imported or autochthonous, but it is evident that the incidence of alveolar echinococcosis is rising in Europe. Due to its rareness and malignant nature of the disease, it is often misdiagnosed or diagnosed late when radical surgical treatment is impossible to perform. Clinicians should be aware of this emerging parasitic disease, especially in immunocompromised patients, because every delay in reaching the diagnosis seriously hampers therapeutic efficacy. Better therapeutic options and standardized guidelines on the modulation of immunosuppressive therapy in these patients are highly needed. 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

In this paper, an alignment-free bioinformatics technique, termed the 20D-Dynamic Representation of Protein Sequences, is utilized to investigate the similarity/dissimilarity between Baculovirus and Echinococcus multilocularis genome sequences. In this method, amino acid sequences are depicted as 20D-dynamic graphs, comprising sets of “material points” in a 20-dimensional space. The spatial distribution of these material points is indicative of the sequence characteristics and is quantitatively described by sequence descriptors akin to those employed in dynamics, such as coordinates of the center of mass of the 20D-dynamic graph and the tensor of the moment of inertia of the graph (defined as a symmetric matrix). Each descriptor unveils distinct features of similarity and is employed to establish similarity relations among the examined sequences, manifested either as a symmetric distance matrix (“similarity matrix”), a classification map, or a phylogenetic tree. The classification maps are introduced as a new way of visualizing the similarity relations obtained using the 20D-Dynamic Representation of Protein Sequences. Some classification maps are obtained using the Principal Component Analysis (PCA) for the center of mass coordinates and normalized moments of inertia of 20D-dynamic graphs as input data. Although the method operates in a multidimensional space, we also apply some visualization techniques, including the projection of 20D-dynamic graphs onto a 2D plane. Studies on model sequences indicate that the method is of high quality, both graphically and numerically. Despite the high similarity observed among the sequences of E. multilocularis, subtle discrepancies can be discerned on the 2D graphs. Employing this approach has led to the discovery of numerous new similarity relations compared to our prior study conducted at the DNA level, using the 4D-Dynamic Representation of DNA/RNA Sequences, another alignment-free bioinformatics method also introduced by us. Full article