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Keywords = human alveolar echinococcosis

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16 pages, 4847 KB  
Article
Localization of the Complement C1q-Binding Site on Echinococcus multilocularis Calreticulin Identified by Peptide Mapping
by Yinghui Song, Meng Xia, Haoran Zong, Wenjie Dong, Qiang Wang, Qin Yang, Bin Zhan, Yanhai Wang and Limei Zhao
Trop. Med. Infect. Dis. 2026, 11(6), 146; https://doi.org/10.3390/tropicalmed11060146 - 26 May 2026
Viewed by 209
Abstract
Alveolar echinococcosis is a life-threatening zoonotic parasitic disease caused by infection of Echinococcus multilocularis larvae. To survive within the host’s immune milieu, E. multilocularis has evolved sophisticated immune evasion strategies, including the expression of immunomodulatory proteins that regulate the host immune response. Our [...] Read more.
Alveolar echinococcosis is a life-threatening zoonotic parasitic disease caused by infection of Echinococcus multilocularis larvae. To survive within the host’s immune milieu, E. multilocularis has evolved sophisticated immune evasion strategies, including the expression of immunomodulatory proteins that regulate the host immune response. Our previous studies have demonstrated that E. multilocularis calreticulin (EmCRT) possessed strong binding ability to human complement component C1q to inhibit C1q-initiated complement activation and biological functions. To further elucidate the mechanism by which EmCRT mediates C1q inactivation and immune evasion, the precise C1q-binding site on EmCRT was identified and analyzed in this study through expression of overlapping fragments and synthesis of overlapping peptides covering the identified functional fragment. The fragment expression and functional assay narrowed down the C1q-binding site to the EmCRT-S1 fragment located between amino acids 140 and 204 of EmCRT. The precise binding site was further pinpointed to the P5 peptide (EmCRT160–174 aa) by testing the synthetic peptides covering this region. The binding of peptide P5 to C1q markedly suppressed the activation of the C1q-mediated classical complement pathway and C1q-induced neutrophil chemotaxis, production of reactive oxygen species, cathepsin G, and myeloperoxidase. These findings suggest that the C1q-binding P5 peptide of EmCRT may serve as a potential target for the development of vaccines against echinococcosis or therapeutic drugs for complement-associated inflammatory or autoimmune diseases. Full article
(This article belongs to the Special Issue Research Advances and New Perspectives on Helminthic Diseases)
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11 pages, 257 KB  
Article
Hunting and Stray Dogs as Reservoirs of Echinococcus Species
by Nikola Betić, Milica Kuručki, Katarina Breka, Aleksandra Penezić, Neda Bogdanović, Ilija Pantelić, Ana Vuletić, Tijana Kukurić, Jelena Karanović, Jovana Raičević, Aleksandar Bajčić, Ivana Klun and Aleksandra Uzelac
Animals 2026, 16(9), 1421; https://doi.org/10.3390/ani16091421 - 6 May 2026
Viewed by 380
Abstract
In Serbia, human echinococcosis cases are predominantly diagnosed as the cystic form, caused by Echinococcus granulosus sensu lato (s. l.) complex tapeworms. Alveolar echinococcosis, a more severe disease caused by Echinococcus multilocularis, emerged recently. Domestic dogs have been implicated in [...] Read more.
In Serbia, human echinococcosis cases are predominantly diagnosed as the cystic form, caused by Echinococcus granulosus sensu lato (s. l.) complex tapeworms. Alveolar echinococcosis, a more severe disease caused by Echinococcus multilocularis, emerged recently. Domestic dogs have been implicated in the transmission of E. granulosus sensu stricto G1/3 to humans. In an ongoing screening of definitive hosts for the presence of Echinococcus spp. to discover reservoirs of E. multilocularis, fecal samples of hunting (n = 29) and stray dogs (n = 66) were examined. Taeniid eggs were collected using flotation and mesh filtration. The presence of Cyclophyllidea, E. granulosus s. l. and E. multilocularis DNA was detected by specific PCR assays. In total, 60% of the fecal samples contained cyclophyllidean DNA, while Echinococcus spp. DNA was detected in 7.4% of the samples. E. canadensis G6–8,10 DNA was present in 4.2% and E. multilocularis in 3.2% of the samples. E. multilocularis DNA was detected only in stray dog feces, suggesting that strays are a reservoir and possibly an important link in the transmission chain. To the best of our knowledge, this study provides the first molecular identification of Echinococcus spp. in dogs in Serbia. Full article
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10 pages, 4880 KB  
Systematic Review
Prevalence of Liver Cystic Echinococcosis in Türkiye: A Systematic Review of Population-Based Ultrasound Imaging Surveys
by Cuneyt Kayaalp, Basak Kayaalp, Cemalettin Aydin and Servet Karagul
Pathogens 2026, 15(5), 496; https://doi.org/10.3390/pathogens15050496 - 4 May 2026
Viewed by 307
Abstract
Background: Cystic echinococcosis (CE) is a chronic zoonotic parasitic disease with a significant impact on public health in endemic regions. The liver is the most frequently affected organ, and ultrasound-based surveys are considered a reliable tool for detecting asymptomatic infections. As population-based [...] Read more.
Background: Cystic echinococcosis (CE) is a chronic zoonotic parasitic disease with a significant impact on public health in endemic regions. The liver is the most frequently affected organ, and ultrasound-based surveys are considered a reliable tool for detecting asymptomatic infections. As population-based data specifically addressing hepatic CE prevalence in Türkiye remain limited, we aimed to assess the prevalence of liver cystic echinococcosis in Türkiye using only ultrasound-based surveys. Methods: A systematic review was conducted, in accordance with the PRISMA guidelines, to estimate the prevalence of liver CE in Türkiye based exclusively on ultrasound-based field surveys. Electronic databases (PubMed and Scopus) were searched up to March 2026. Eligible studies included population-based human screening surveys reporting hepatic CE prevalence confirmed via ultrasonography. Data were extracted and descriptively pooled, with subgroup analyses performed according to age group (children vs. adults) and residential setting (urban vs. rural). The protocol was prospectively registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY; registration Number: INPLASY202630029). Only human ultrasound-based screening studies including liver CE data were accepted; alveolar echinococcosis studies were excluded. Pooled prevalence estimates with 95% confidence intervals (CIs) were calculated using a random-effects model, and between-study heterogeneity was assessed with the I2 statistic. Results: We analyzed the data of 23,154 people from 11 different provinces reported in 8 studies. The overall pooled liver CE prevalence was 0.31% (95% CI: 0.14–0.54), while it was 0.12% and 0.43% for urban and rural residents, respectively. Adults had higher prevalence of liver CE than children (0.43% vs. 0.16%). When separated by both living area and age, the prevalence rates were as follows: urban children 0.07%, urban adults 0.21%, rural children 0.29% and rural adults 0.60%. Conclusions: This is the first systematic review evaluating the prevalence of liver CE in Türkiye exclusively from ultrasound-based studies. While the overall prevalence of liver CE was 0.31%, adults living in rural areas presented a nearly two-fold higher rate (0.60%). Ultrasound-based screening provides a practical and effective approach for epidemiological surveillance. Targeted control strategies—including community-based screening, health education, and veterinary interventions—are essential to reduce transmission and disease burden, particularly in high-risk rural populations. Full article
(This article belongs to the Section Parasitic Pathogens)
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12 pages, 1784 KB  
Case Report
Profile of Cytokines TNFα, IL-1β, IL-6, IL-4, and IL-10 in Relation to Disease Progression in a Patient with Advanced Liver Alveolar Echinococcosis and Non-Optimal Antiparasitic Treatment: Four-Year Follow-Up
by Katarzyna Zorena, Małgorzata Sulima, Beata Szostakowska, Barbara Siewert and Katarzyna Sikorska
Pathogens 2025, 14(10), 957; https://doi.org/10.3390/pathogens14100957 - 23 Sep 2025
Cited by 2 | Viewed by 1731
Abstract
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, [...] Read more.
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
(This article belongs to the Special Issue Parasitic Diseases in the Contemporary World)
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16 pages, 1357 KB  
Article
EmsB Microsatellite Analysis of Echinococcus multilocularis Specimens Isolated from Belgian Patients with Alveolar Echinococcosis and from Animal Hosts
by Sabrina Egrek, Jenny Knapp, Rosalie Sacheli, Khalid El Moussaoui, Philippe Léonard, Eva Larranaga Lapique, Laurence Millon, Sara Engelskirchen, Olivier Detry, Annick Linden and Marie-Pierre Hayette
Pathogens 2025, 14(6), 584; https://doi.org/10.3390/pathogens14060584 - 12 Jun 2025
Viewed by 1417
Abstract
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 [...] Read more.
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
(This article belongs to the Section Parasitic Pathogens)
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16 pages, 2395 KB  
Review
Human Echinococcosis in the Russian Federation in the 21st Century: A Systematic Review
by Branko Bobić, Tijana Štajner, Vladimir Ćirković, Jelena Srbljanović, Olivera Lijeskić, Neda Bauman and Đorđe Zlatković
Microorganisms 2025, 13(5), 1122; https://doi.org/10.3390/microorganisms13051122 - 14 May 2025
Cited by 1 | Viewed by 1181
Abstract
According to the WHO, echinococcosis is a neglected tropical disease of global importance. The Russian Federation (R.F.) is traditionally considered an endemic area of echinococcosis. This study aims to analyze the state of human infection in the R.F. in the 2000–2021 period, for [...] Read more.
According to the WHO, echinococcosis is a neglected tropical disease of global importance. The Russian Federation (R.F.) is traditionally considered an endemic area of echinococcosis. This study aims to analyze the state of human infection in the R.F. in the 2000–2021 period, for which there is not enough consolidated data. Epidemiological data on human echinococcosis in the R.F. from 1 January 2000 to 31 December 2021 were collected through literature research (both published and grey literature) and official reports. From the 2022 selected records, 12 full-text articles, three doctoral dissertations, and 17 official reports were analyzed, all of which met the criteria for inclusion in the study. In the R.F., in the period from 2000 to 2021, echinococcosis (cystic (C.E.) and alveolar (A.E.) echinococcosis) has been continuously registered in humans (0.4–0.22 cases/100,000 inhabitants). Until 2013, the incidence of echinococcosis did not change (Pearson’s r (N = 13) = 0.288, p = 0.340), but in the period 2013–2021 it decreased significantly (Pearson’s r (N = 9) = −0.709, p = 0.032). In that period, the incidence of C.E. decreased significantly (Pearson’s r (N = 9) = −0.717, p = 0.035), while the incidence of A.E. did not change (Pearson’s r (N = 9) = −0.518, p = 0.154). The infection is registered annually in 30 out of 86 federal units. The C.E. infection rate was significantly higher in the European part (0.46/100,000 population) (2 = 33,783. r < 0.00001) than in the Asian part of the R.F. (0.32/100,000 population), where A.E. was more widespread. Within the European part, the frequency of C.E. infection was significantly higher in the southern (0.70/100,000 inhabitants) (χ2 = 806.67, p < 00001) than in the central and northern parts (0.25/100,000 inhabitants). The incidence of C.E. per federal district was positively correlated with rural population representation (Pearson’s r (N = 8) = 0.866, p = 0.005). Every year, although in small numbers, deaths caused by echinococcosis (in the period 2009–2020—66 deaths) were registered in the R.F., significantly more often caused by A.E. than C.E. (χ2 = 39.4401, p < 0.00001). Our results indicate that, between 2000 and 2021, echinococcosis was still generally endemic in the R.F. The incidence of C.E. has demonstrated a decreasing trend, especially after 2014, while the rate of A.E. remained unchanged. Full article
(This article belongs to the Special Issue Infectious Diseases: New Approaches to Old Problems, 3rd Edition)
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15 pages, 2682 KB  
Article
Echinococcus multilocularis Calreticulin Inhibits Lectin Pathway of Complement Activation by Directly Binding to Mannose-Binding Lectin
by Yuxiao Shao, Meng Xia, Yinghui Song, Yan Yan, Xiaofang Dong, Haoran Zong, Bin Zhan, Yanhai Wang and Limei Zhao
Pathogens 2025, 14(4), 354; https://doi.org/10.3390/pathogens14040354 - 5 Apr 2025
Cited by 3 | Viewed by 1605
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Immunity and Immunoregulation in Helminth Infections)
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11 pages, 1227 KB  
Case Report
Double Trouble on the Lower Leg—Unique Human Coinfection with Echinococcus granulosus and Echinococcus multilocularis Without Liver Involvement
by David Beck, Mirjana Balen Topić, Klaudija Višković, Neven Papić, Rado Žic, Mario Sviben, Tomislav Meštrović, Adrijana Baković Kovačević and Relja Beck
Pathogens 2025, 14(4), 343; https://doi.org/10.3390/pathogens14040343 - 3 Apr 2025
Cited by 4 | Viewed by 2611
Abstract
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 [...] Read more.
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
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15 pages, 1572 KB  
Review
Human Alveolar Echinococcosis—A Neglected Zoonotic Disease Requiring Urgent Attention
by Ali Rostami, Britta Lundström-Stadelmann, Caroline F. Frey, Guido Beldi, Anja Lachenmayer, Bill C. H. Chang, Mohammad Mobin Norouzian, Andrew Hemphill and Robin B. Gasser
Int. J. Mol. Sci. 2025, 26(6), 2784; https://doi.org/10.3390/ijms26062784 - 19 Mar 2025
Cited by 14 | Viewed by 4769
Abstract
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. [...] Read more.
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
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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12 pages, 2224 KB  
Article
Rapid Discriminative Identification of the Two Predominant Echinococcus Species from Canine Fecal Samples in the Tibetan Region of China by Loop-Mediated Isothermal Amplification–Lateral Flow Dipstick Assay
by Xinyue Lv, Jiajia Ai, Xiaojin Mo, Haojie Ding, Sofia Litchev, Entung Lu, Youhong Weng, Qing He, Quzhen Gongsang, Shijie Yang, Xiumin Ma, Jingzhong Li, Huasheng Pang, Shaohong Lu and Qingming Kong
Trop. Med. Infect. Dis. 2024, 9(6), 136; https://doi.org/10.3390/tropicalmed9060136 - 20 Jun 2024
Cited by 2 | Viewed by 2281
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Echinococcosis: From Parasite–Host Interaction to Rapid Detection)
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23 pages, 37609 KB  
Article
Efficacy and Safety of Asparagusic Acid against Echinococcus multilocularis In Vitro and in a Murine Infection Model
by Zhuanhong Lu, Yating Wang, Chuanchuan Liu and Haining Fan
Trop. Med. Infect. Dis. 2024, 9(5), 110; https://doi.org/10.3390/tropicalmed9050110 - 11 May 2024
Cited by 2 | Viewed by 2625
Abstract
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 [...] Read more.
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
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11 pages, 768 KB  
Article
Serological Comparison of Native Antigen ELISAs with Rapid ICT Test Kits for the Diagnosis of Human Alveolar and Cystic Echinococcosis in China
by Shu-Kun Yang, Wei Zhang, Na Zhu, Donald P. McManus, Darren J. Gray, Archie C. A. Clements, Angela M. Cadavid Restrepo, Gail M. Williams, Ting Zhang, Guo-Rong Ma, Yan-Hui Yang and Yu-Rong Yang
Trop. Med. Infect. Dis. 2024, 9(2), 44; https://doi.org/10.3390/tropicalmed9020044 - 7 Feb 2024
Cited by 6 | Viewed by 3443
Abstract
Background: The aim of this study was to compare the diagnostic performance of native antigen ELISAs and ADAMU-AE/CE commercial ICT test kits in subjects either exposed to Echinococcus infection or with clinically diagnosed alveolar (AE) or cystic (CE) echinococcosis. Methods: A total of [...] Read more.
Background: The aim of this study was to compare the diagnostic performance of native antigen ELISAs and ADAMU-AE/CE commercial ICT test kits in subjects either exposed to Echinococcus infection or with clinically diagnosed alveolar (AE) or cystic (CE) echinococcosis. Methods: A total of 370 subjects with a previous clinical confirmation of CE or AE from northwestern China were recruited. Serum samples were also obtained from 3923 children/teenagers during a community survey. All sera were tested using native antigen ELISAs. The ADAMU-AE/CE test kits were subsequently used for the serology of the 370 clinically confirmed individuals and of 251 children/teenagers that were ELISA antibody-positive for both Echinococcus species but ultrasound-negative during baseline survey. An analysis of the association between the serological tests and ultrasound classification was carried out amongst 89 AE and 164 CE cases. A Kappa consistency analysis was undertaken to compare the diagnostic performance of the native antigen ELISAs and the ADAMU kits and the ultrasound imaging results. The χ² test was also used for a comparison of the different seropositivity rates between the groups. Findings: There was poor consistency (Kappa = 0.26 and 0.28 for AE and CE respectively) between the native antigen ELISAs and the ADAMU kits for the diagnosis of AE and CE among the cases and the surveyed children/teenagers, but a relatively good consistency (Kappa = 0.63) between the ADAMU-AE kit and ultrasound observations for the AE cases. Additionally, of the 251 teenagers co-positive for both AE and CE antibodies by the native antigen ELISAs, only one was found positive by the ADAMU-AE kit, verified as a new AE case on subsequent ultrasound follow-up. The remainder (N = 250) were negative by serology using the ADAMU-AE/CE kits and by ultrasound examination. The two native antigen ELISAs did not discriminate well between cases of clinically diagnosed AE and CE. In contrast, ADAMU-AE and ADAMU-CE commercial ICT test kits readily differentiated cases of AE from CE with specificities of 99% for AE and 100% for CE. Conclusions: The ADAMU-AE/CE kits proved reliable, accurate, and amenable diagnostic tools in the clinical setting for confirmation of suspected AE/CE cases. The native antigen ELISAs tests can provide useful information on the level of human exposure to Echinococcus infection. Full article
(This article belongs to the Special Issue Echinococcosis: From Parasite–Host Interaction to Rapid Detection)
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7 pages, 830 KB  
Brief Report
Emergence of Echinococcus multilocularis in Central Continental Croatia: A Human Case Series and Update on Prevalence in Foxes
by Mirjana Balen Topić, Neven Papić, Klaudija Višković, Mario Sviben, Tajana Filipec Kanižaj, Stipislav Jadrijević, Daria Jurković and Relja Beck
Life 2023, 13(6), 1402; https://doi.org/10.3390/life13061402 - 16 Jun 2023
Cited by 17 | Viewed by 3366
Abstract
Human alveolar echinococcosis (HAE), caused by the metacestode stage of Echinococcus multilocularis, has emerged in many European countries over the last two decades. Here, we report the first data on the new HAE focus with increasing incidence in central Croatia, describe its [...] Read more.
Human alveolar echinococcosis (HAE), caused by the metacestode stage of Echinococcus multilocularis, has emerged in many European countries over the last two decades. Here, we report the first data on the new HAE focus with increasing incidence in central Croatia, describe its clinical presentation and outcomes in diagnosed patients, and provide an update on the prevalence and geographic distribution of Echinococcus multilocuaris in red foxes. After the initial case in 2017 from the eastern state border, from 2019 to 2022, five new autochthonous HAE cases were diagnosed, all concentrated in the Bjelovar-Bilogora County (the county incidence in 2019 and 2021: 0.98/105, in 2022: 2.94/105/year; prevalence for 2019–2022: 4.91/105). The age range among four female and two male patients was 37–67 years. The patients’ liver lesions varied in size from 3.1 to 15.5 cm (classification range: P2N0M0–P4N1M0), and one patient had dissemination to the lungs. While there were no fatalities, postoperative complications in one patient resulted in liver transplantation. In 2018, the overall prevalence of red foxes was 11.24% (28/249). A new focus on HAE has emerged in central continental Croatia, with the highest regional incidence in Europe. Screening projects among residents and the implementation of veterinary preventive measures following the One Health approach are warranted. Full article
(This article belongs to the Special Issue Emerging and Re-emerging Zoonotic Infectious Diseases)
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20 pages, 2354 KB  
Article
Circulating Small RNA Profiling of Patients with Alveolar and Cystic Echinococcosis
by Marcela A. Cucher, Mara Mariconti, Tommaso Manciulli, Ambra Vola, Mara C. Rosenzvit, Klaus Brehm, Laura Kamenetzky and Enrico Brunetti
Biology 2023, 12(5), 715; https://doi.org/10.3390/biology12050715 - 13 May 2023
Cited by 6 | Viewed by 2827
Abstract
Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, serology, and clinical and epidemiological data. However, [...] Read more.
Alveolar (AE) and cystic (CE) echinococcosis are two parasitic diseases caused by the tapeworms Echinococcus multilocularis and E. granulosus sensu lato (s. l.), respectively. Currently, AE and CE are mainly diagnosed by means of imaging techniques, serology, and clinical and epidemiological data. However, no viability markers that indicate parasite state during infection are available. Extracellular small RNAs (sRNAs) are short non-coding RNAs that can be secreted by cells through association with extracellular vesicles, proteins, or lipoproteins. Circulating sRNAs can show altered expression in pathological states; hence, they are intensively studied as biomarkers for several diseases. Here, we profiled the sRNA transcriptomes of AE and CE patients to identify novel biomarkers to aid in medical decisions when current diagnostic procedures are inconclusive. For this, endogenous and parasitic sRNAs were analyzed by sRNA sequencing in serum from disease negative, positive, and treated patients and patients harboring a non-parasitic lesion. Consequently, 20 differentially expressed sRNAs associated with AE, CE, and/or non-parasitic lesion were identified. Our results represent an in-depth characterization of the effect E. multilocularis and E. granulosus s. l. exert on the extracellular sRNA landscape in human infections and provide a set of novel candidate biomarkers for both AE and CE detection. Full article
(This article belongs to the Special Issue Roles and Use of Extracellular Vesicles in Health and Disease)
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11 pages, 298 KB  
Article
Molecular Screening of Echinococcus spp. and Other Cestodes in Wild Carnivores from Central Italy
by Silvia Crotti, Leonardo Brustenga, Deborah Cruciani, Piero Bonelli, Nicoletta D’Avino, Andrea Felici, Benedetto Morandi, Carla Sebastiani, Sara Spina and Marco Gobbi
Vet. Sci. 2023, 10(5), 318; https://doi.org/10.3390/vetsci10050318 - 27 Apr 2023
Cited by 6 | Viewed by 3950
Abstract
Tapeworm infections are among the most relevant parasitic diseases in humans and animals. Tapeworms from the Genus Echinococcus are particularly important as they can cause cystic or alveolar echinococcosis. A molecular screening was performed on 279 fecal samples collected from carcasses of wild [...] Read more.
Tapeworm infections are among the most relevant parasitic diseases in humans and animals. Tapeworms from the Genus Echinococcus are particularly important as they can cause cystic or alveolar echinococcosis. A molecular screening was performed on 279 fecal samples collected from carcasses of wild carnivores from Central Italy using PCR targeting diagnostic fragments of nad1, rrnS, and nad5 genes. Samples positive for either Taenia spp. or Echinococcus granulosus were sequenced to taxonomically identify the parasitic DNA. Of the 279 samples, 134 (48.0%) gave positive results in the multiplex PCR. Only one (0.4%) sample from an Apennine wolf tested positive for Echinococcus granulosus sensu stricto (genotype G3), whereas no sample tested positive for E. multilocularis. The most frequently detected tapeworms were: Mesocestoides corti (syn M. vogae) (12.9%), M. litteratus (10.8%), Taenia serialis (9.3%), and T. hydatigena (6.5%), other tapeworms were rarely detected. The results suggest that Echinococcus infections in Central Italy do not seem to be sustained by sylvatic cycles, confirming the absence of E. multilocularis in Central Italy. The survey corroborates, yet again, the importance of passive surveillance of wild animals that can serve as reservoirs for zoonotic pathogens, especially on wild canids that in other areas are strongly implicated in the transmission of E. granulosus and E. multilocularis. Full article
(This article belongs to the Special Issue Echinococcosis)
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