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Rostami A, Lundström-Stadelmann B, Frey CF, Beldi G, Lachenmayer A, Chang BCH, Norouzian MM, Hemphill A, Gasser RB. Human Alveolar Echinococcosis-A Neglected Zoonotic Disease Requiring Urgent Attention. Int J Mol Sci 2025; 26:2784. [PMID: 40141427 PMCID: PMC11943292 DOI: 10.3390/ijms26062784] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 03/09/2025] [Accepted: 03/13/2025] [Indexed: 03/28/2025] Open
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. 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.
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Affiliation(s)
- Ali Rostami
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; (A.R.); (M.M.N.)
| | - Britta Lundström-Stadelmann
- Multidisciplinary Center for Infectious Diseases, University of Bern, Hallerstrasse 6, 3012 Bern, Switzerland; (B.L.-S.); (G.B.)
- Reference Laboratory of Federal Office for Food Safety and Veterinary Affairs, Institute of Parasitology and Echinococcus, University of Bern, Länggassstrasse 122, 3012 Bern, Switzerland;
| | - Caroline F. Frey
- Reference Laboratory of Federal Office for Food Safety and Veterinary Affairs, Institute of Parasitology and Echinococcus, University of Bern, Länggassstrasse 122, 3012 Bern, Switzerland;
| | - Guido Beldi
- Multidisciplinary Center for Infectious Diseases, University of Bern, Hallerstrasse 6, 3012 Bern, Switzerland; (B.L.-S.); (G.B.)
- Department for Visceral Surgery and Medicine, Bern University Hospital, University of Bern, 3010 Bern, Switzerland;
- Department for Biomedical Research, Bern University Hospital, University of Bern, 3008 Bern, Switzerland
| | - Anja Lachenmayer
- Department for Visceral Surgery and Medicine, Bern University Hospital, University of Bern, 3010 Bern, Switzerland;
| | - Bill C. H. Chang
- Department of Veterinary Biosciences, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia;
| | - Mohammad Mobin Norouzian
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran; (A.R.); (M.M.N.)
| | - Andrew Hemphill
- Reference Laboratory of Federal Office for Food Safety and Veterinary Affairs, Institute of Parasitology and Echinococcus, University of Bern, Länggassstrasse 122, 3012 Bern, Switzerland;
| | - Robin B. Gasser
- Department of Veterinary Biosciences, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, Australia;
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Kronenberg PA, Laurimäe T, Reinehr M, Deibel A, Hasler S, Gehrig P, Weber A, Deplazes P, Eichenberger RM. Identification and characterization of the elusive protein backbone of the immuno-dominant and species-specific Em2(G11) metacestode antigen of Echinococcus multilocularis. FRONTIERS IN PARASITOLOGY 2025; 4:1540215. [PMID: 40135073 PMCID: PMC11935348 DOI: 10.3389/fpara.2025.1540215] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 02/20/2025] [Indexed: 03/27/2025]
Abstract
Alveolar echinococcosis (AE) caused by Echinococcus multilocularis, is a severe zoonotic disease in humans. One of the major metacestode antigens of E. multilocularis is the Em2 or Em2(G11) native purified antigen. The Em2 antigen is used for the serological and histopathological diagnosis of AE in humans and plays an important role in parasite-host interactions. As the Em2(G11) antigen is a mucin-type and glycosylated protein, the protein backbone has not been identified yet. We have targeted the protein backbone identification through mass spectrometry (LC-MS/MS) analysis of the Em2(G11) antigen. As a result, we evidenced that the Em2(G11) antigen consists of 33 unique protein candidates of which the most abundant was ''EmuJ_001105600.1''. This protein (889 amino acids) had 427 predicted glycosylation sites. Amino acid composition comparison was in agreement with earlier studies and further confirmed the candidate of interest as the most likely Em2(G11) protein backbone. NCBI BLAST revealed no other known protein homologues in related Echinococcus species nor helminths. After successfully producing this protein recombinantly (Em2rec), a monoclonal antibody (mAbEm2rec) was raised against it. Immunohistochemical stainings of liver tissue sections of AE patients showed that the mAbEm2rec reacts specifically with E. multilocularis antigens solely after deglycosylation with an O-glycosidase cocktail. Similarly, in ELISA, the mAbEm2rec recognized the recombinant and native antigens of E. multilocularis after deglycosylation. These results reveal the nature of this highly glycosylated and specific protein, where mucins are covering the proteomic backbone. For antibody detection in human patients, the native Em2(G11) antigen was superior compared to the Em2rec antigen, indicating the importance of glycosylated epitopes in this immuno-dominant antigen. Of note is the second most abundant protein in the Em2(G11) antigen, namely phosphoenolpyruvate carboxykinase (PEPCK; EmuJ_000292700.1). PEPCK is known to play an important part in the metabolic pathway of gluconeogenesis in E. multilocularis. However, whether this co-eluted protein has any functional importance in the parasite-host interplay of nutrients, growth, and diagnostic significance, is not explored. By combining various approaches, we were able to uncover and confirm the protein backbone of the diagnostic Em2(G11) antigen of E. multilocularis.
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Affiliation(s)
- Philipp A. Kronenberg
- Institute of Parasitology, Vetsuisse and Medical Faculty, University of Zurich, Zurich, Switzerland
- Medical Micro- and Molecular Biology, Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences (ZHAW), Wädenswil, Switzerland
| | - Teivi Laurimäe
- Institute of Parasitology, Vetsuisse and Medical Faculty, University of Zurich, Zurich, Switzerland
- Department of Zoology, Institute of Ecology and Earth Sciences, University of Tartu, Tartu, Estonia
| | - Michael Reinehr
- Department of Pathology and Molecular Pathology, University of Zurich and University Hospital Zurich, Zurich, Switzerland
- Institute of Pathology, Hegau-Bodensee Clinic, Gesundheitsverband Landkreis Konstanz (GLKN), Singen, Germany
| | - Ansgar Deibel
- Departement for Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Sina Hasler
- Institute of Parasitology, Vetsuisse and Medical Faculty, University of Zurich, Zurich, Switzerland
| | - Peter Gehrig
- Functional Genomics Center Zurich, University of Zurich and Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland
| | - Achim Weber
- Department of Pathology and Molecular Pathology, University of Zurich and University Hospital Zurich, Zurich, Switzerland
| | - Peter Deplazes
- Institute of Parasitology, Vetsuisse and Medical Faculty, University of Zurich, Zurich, Switzerland
- Departement for Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland
| | - Ramon M. Eichenberger
- Institute of Parasitology, Vetsuisse and Medical Faculty, University of Zurich, Zurich, Switzerland
- Medical Micro- and Molecular Biology, Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences (ZHAW), Wädenswil, Switzerland
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Kley AC, White AC. Parasitic Infections in Pulmonary and ICU Patients: Presentation, Diagnosis, and Treatment. Chest 2025; 167:686-693. [PMID: 39521374 DOI: 10.1016/j.chest.2024.10.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 10/02/2024] [Accepted: 10/08/2024] [Indexed: 11/16/2024] Open
Abstract
Parasitic infections in the United States are mostly seen in immigrants and travelers. In many cases, pulmonary and intensive care physicians fail to consider parasitic disease, which can result in delayed diagnosis and adverse outcomes. Almost 2,000 cases of imported malaria are diagnosed in the United States each year. Severe cases can be confused with bacterial sepsis (shock, lactic acidosis, pneumonia, renal failure, respiratory failure, and jaundice). In contrast to bacterial sepsis, survival is improved by restrictive fluid therapy. Parenteral artesunate is licensed to treat severe cases but may not be readily accessible. Strongyloidiasis is endemic in warm and most tropical regions. Chronic strongyloidiasis causes few symptoms and can persist for decades after the patient leaves the endemic region. Treatment with corticosteroids may lead to hyperinfection, which may present with bacteremia and meningitis caused by enteric organisms, pulmonary hemorrhage, and gastrointestinal pain, bleeding, or obstruction. Treatment with ivermectin can be curative if initiated early. Cystic echinococcosis can present as pulmonary mass. Paragonimus presents with hemoptysis, pulmonary nodules, or pleural effusions, and usually with eosinophilia. Endemic regions include not only East Asia but also Southeast Asia, West Africa, the Pacific coast of Latin America, and even North America. Other parasitic infections can involve the lungs. This article aims to provide awareness of the most clinically relevant parasitic infections seen in pulmonary and critical care medicine.
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Affiliation(s)
- Adam C Kley
- Section of Pulmonary, Critical Care and Sleep Medicine, Baylor College of Medicine, Houston, TX
| | - A Clinton White
- Infectious Diseases Division, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX.
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Akyuz M, Avcioglu H. Evaluation of the prevalence of Echinococcus multilocularis in free-roaming dogs in the human alveolar echinococcosis endemic region of Turkey. Acta Trop 2025; 264:107560. [PMID: 39971080 DOI: 10.1016/j.actatropica.2025.107560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Revised: 02/11/2025] [Accepted: 02/16/2025] [Indexed: 02/21/2025]
Abstract
As free-roaming dogs may play a pivotal role in the transmission of alveolar echinococcosis (AE) to humans, the detection of the parasite in dogs is important for the control of the disease. The objective of this study was to ascertain the current situation of E. multilocularis in free-roaming dogs in the northeastern region of Türkiye which is endemic for human AE. The study area comprises the provinces of Ağrı, Ardahan, Bayburt, Erzincan, Erzurum, Iğdır and Kars. Between 2019 and 2020, 1069 individual fecal samples collected from free-roaming dogs were analyzed by sequential flotation/sieving method. Each taeniid egg-positive sample was then subjected to PCR for the amplification of partial fragments of 12S rRNA and NAD1 of E. multilocularis. The regional prevalence of E. multilocularis was 8.7 % (93/1069), while the rates of provinces were as follows: Bayburt [14.4 % (15/104)], Iğdır [13.2 % (14/106)], Kars [10.4 % (12/115)], Erzurum [8.3 % (35/420)], Erzincan [6.9 % (7/101)], Ağrı [6.9 % (8/116)] and Ardahan [1.9 % (2/107)]. This study demonstrates the high burden of E. multilocularis in free-roaming dogs and highlights the potential crucial role of dogs in the transmission of AE, which is a significant public health concern for humans in the region. These findings emphasize the necessity to design control strategies for AE in the region that cover both rural and urban areas and focus specifically on free-roaming dogs.
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Affiliation(s)
- Muzaffer Akyuz
- Department of Parasitology, Faculty of Veterinary Medicine, Atatürk University, Erzurum 25240, Türkiye.
| | - Hamza Avcioglu
- Department of Parasitology, Faculty of Veterinary Medicine, Atatürk University, Erzurum 25240, Türkiye
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Najjari M, Manesh AD, Rezaeian S, Farrash BRH, Mohammadi MA, Ebrahimipour M. A ten-year evaluation of central nervous system cystic echinococcosis in a highly endemic area of Iran: Molecular epidemiology and clinicopathological characteristics. Parasite Epidemiol Control 2025; 28:e00414. [PMID: 39968324 PMCID: PMC11833634 DOI: 10.1016/j.parepi.2025.e00414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2024] [Revised: 12/16/2024] [Accepted: 01/26/2025] [Indexed: 02/20/2025] Open
Abstract
Cystic echinococcosis can involve various organs in humans with the brain and spine being particularly vulnerable. This research aimed to study clinicopathological features and molecular analysis of the central nervous system (CNS) echinococcosis cases in a central hospital for hydatid cyst surgery in northeastern Iran. CNS echinococcosis cases from surgically managed human CE cases at Ghaem hospital in northeastern Iran were analyzed from 2012 to 2022. Demographic and clinicopathological data were collected for CNS echinococcosis cases and formalin-fixed paraffin-embedded (FFPE) blocks were used for molecular analysis. The total prevalence of CNS echinococcosis cases was 1. 8 %. Most of the CE cases were reported in women (64. 7 %) and from rural areas (58. 8 %). The highest number of cases (41. 2 %) were aged ≤18 years, with majority being ranchers (47. 1 %). Thirteen cases (76.5 %) were found to have cysts in their brain, particularly in the supratentorial site. Headache was the most commonly reported sign in cases (9/13, 69.2 %). Infiltration of eosinophils, polymorphic inflammatory cells, and giant cells, gliosis, and foreign body granulomatous reaction, along with mild infiltration of mononuclear cells showing degeneration and necrotic foci in the brain infections. Spine infections included bone cartilage, ligaments, and hydatid cyst wall fragments. PCR analysis conducted on 17 samples revealed the presence of 13 isolates of E. granulosus sensu lato. Among these, 11 were classified within the E. granulosus sensu stricto (G1 and/or G3) complex, while 2 isolates were identified as belonging to the E. canadensis G6/G7. Cerebrospinal infection is a significant aspect of CE cases in northcentral Iran, with a higher prevalence among women and in rural areas. Children were the most affected age group, with the E. granulosus s.s. genotypes being the most common.
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Affiliation(s)
- Mohsen Najjari
- Department of Parasitology and Mycology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Ghaem Educational, Research and Treatment Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Dehesht Manesh
- Department of Parasitology and Mycology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Shahab Rezaeian
- Infectious Diseases Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Bibi Razieh Hosseini Farrash
- Department of Parasitology and Mycology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Ali Mohammadi
- Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Ebrahimipour
- Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran
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Aziz H, Seda P, Aswani Y, Gosse MD, Krishnakumari AJ, Pawlik TM. Cystic echinococcosis of the liver. J Gastrointest Surg 2025; 29:101974. [PMID: 39864780 DOI: 10.1016/j.gassur.2025.101974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 01/18/2025] [Accepted: 01/21/2025] [Indexed: 01/28/2025]
Abstract
BACKGROUND Cystic echinococcosis (CE) is a widely endemic helminthic disease caused by infection with metacestodes (larval stage) of the Echinococcus granulosus tapeworm, which is transmitted by dogs and found on every continent, except Antarctica. This study aimed to review the life cycle, epidemiology, symptoms, diagnostic methods, and treatment of E granulosus infection of the liver. METHODS A comprehensive review was conducted using MEDLINE/PubMed, Google Scholar, Cochrane Library, and the Web of Science, which were accessed between 1990 and 2024. The main search focused on "CE of the liver." The following terms were used: cystic echinococcosis, hydatidosis, E granulosus, echinococcus life cycle, liver cyst, albendazole, liver resection, pericystectomy, cystobiliary fistula, and percutaneous aspiration injection and reaspiration (PAIR). RESULTS CE should be considered in the differential diagnosis of hepatic cysts, especially among individuals with risk factors, such as those who have traveled to or immigrated from areas with a high prevalence. Echinococcus species require 2 hosts to complete their life cycle, with humans acting as intermediate hosts that become infected by ingesting eggs from contaminated environments, leading to cyst formation, typically in the liver or lungs. Symptoms are based on cyst size and location, such as abdominal pain, jaundice, respiratory distress, or neurologic deficits, and can lead to severe complications, such as cyst rupture, allergic reactions, sepsis, or secondary hydatidosis. Imaging plays a key role in evaluating cyst stage, size, location, and potential complications and in determining the appropriateness of a minimally invasive PAIR procedure. Although serum antibody tests typically have a low sensitivity, antigen assays or recombinant proteins may provide useful diagnostic information. For uncomplicated active cysts, the treatment options include chemotherapy alone or in combination with the PAIR technique. CONCLUSION Hepatic echinococcal cysts, which are relatively rare in North America, should be considered in the differential diagnosis of hepatic cysts, especially in individuals with risk factors.
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Affiliation(s)
- Hassan Aziz
- Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, United States.
| | - Peyton Seda
- Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City, IA, United States
| | - Yashant Aswani
- Department of Radiology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States
| | - Matthew D Gosse
- Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States
| | - Aparna Joshi Krishnakumari
- Department of Radiology, King Edward Memorial Hospital and Seth Gordhandas Sunderdas Medical College, Mumbai, India
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, United States
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Wumier W, Abulizi A, Wu P, Jinsihan N, Wang Y, Duysenbi S, Wang Z. Expression of TNF-α, VEGF-A and Microvessel Density in Cerebral Alveolar Echinococcosis and Their Correlation with Perilesional Brain Edema. Acta Parasitol 2025; 70:33. [PMID: 39853563 DOI: 10.1007/s11686-024-00943-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2024] [Accepted: 10/21/2024] [Indexed: 01/26/2025]
Abstract
Alveolar echinococcosis (AE) is an infrequent zoonosis caused by Echinococcus multilocularis with a high degree of disability and mortality. Metastatic cerebral alveolar echinococcosis (CAE) is very rare and the lesions could lead to severe perilesional brain edema (PLBE) and subsequent uncontrollable intracranial hypertension. In this study, we sought to determine the expression of edema-associated factors in CAE lesions and their associations with PLBE. We retrospectively evaluated the clinical data of 18 CAE patients who received craniotomy. Severity of PLBE was described by edema index (EI). Archived specimens were processed for immunohistochemistry to detect tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor A (VEGF-A) and microvessel density (MVD) in CAE lesions. Expression intensity of CAE lesions was quantified by integral optical density (IOD) or count and was compared to the control group. The results showed TNF-α and VEGF-A were significantly expressed in CAE lesions (p < 0.001), their levels were positively correlated with PLBE (TNF-α: r = 0.701, p = 0.001; VEGF-A: r = 0.803, p < 0.001). The MVD of CAE lesions had a similar expression with normal brain tissue, and it was positively correlated with PLBE and VEGF-A (PLBE: r = 0.849, p < 0.001; VEGF-A: r = 0.687, p = 0.002). In conclusion, we speculated the upregulation of TNF-α and VEGF-A induced the formation of PLBE. Besides, though there was no extra increase of MVD, it was still regulated by VEGF-A and provided a better anatomical basis for the formation of PLBE and further promoted it.
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Affiliation(s)
- Wuerken Wumier
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830000, China
- Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Li Yu Shan Road, Xinshi District, Urumqi, 830000, China
| | - Alimasi Abulizi
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830000, China
- Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Li Yu Shan Road, Xinshi District, Urumqi, 830000, China
| | - Pengfei Wu
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830000, China
- Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Li Yu Shan Road, Xinshi District, Urumqi, 830000, China
| | - Najiahai Jinsihan
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830000, China
- Department of Neurosurgery, National Scientific Medical Center, Nur-Sultan, 010000, Kazakhstan
| | - Yongxin Wang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830000, China
- Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Li Yu Shan Road, Xinshi District, Urumqi, 830000, China
| | - Serick Duysenbi
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830000, China.
- Department of Neurosurgery, National Scientific Medical Center, Nur-Sultan, 010000, Kazakhstan.
| | - Zengliang Wang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830000, China.
- Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, No. 137, Li Yu Shan Road, Xinshi District, Urumqi, 830000, China.
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Kaethner M, Zumstein P, Müller J, Preza M, Grossenbacher P, Bartetzko A, Vetter L, Lochner M, Schürch S, Regnault C, Ramírez DV, Lundström-Stadelmann B. Investigation of the threonine metabolism of Echinococcus multilocularis: The threonine dehydrogenase as a potential drug target in alveolar echinococcosis. Int J Parasitol Drugs Drug Resist 2025; 27:100581. [PMID: 39847910 PMCID: PMC11795093 DOI: 10.1016/j.ijpddr.2025.100581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 01/10/2025] [Accepted: 01/12/2025] [Indexed: 01/25/2025]
Abstract
Alveolar echinococcosis (AE) is a severe zoonotic disease caused by the metacestode stage of the fox tapeworm Echinococcus multilocularis. We recently showed that E. multilocularis metacestode vesicles scavenge large amounts of L-threonine from the culture medium. This motivated us to study the effect of L-threonine on the parasite and how it is metabolized. We established a novel metacestode vesicle growth assay with an automated readout, which showed that L-threonine treatment led to significantly increased parasite growth. In addition, L-threonine increased the formation of novel metacestode vesicles from primary parasite cell cultures in contrast to the non-proteinogenic threonine analog 3-hydroxynorvaline. Tracing of [U-13C]-L-threonine and metabolites in metacestode vesicles and culture medium resulted in the detection of [U-13C]-labeling in aminoacetone and glycine, indicating that L-threonine was metabolized by threonine dehydrogenase (TDH). EmTDH-mediated threonine metabolism in the E. multilocularis metacestode stage was further confirmed by quantitative real-time PCR, which demonstrated high expression of emtdh in in vitro cultured metacestode vesicles and also in metacestode samples obtained from infected animals. EmTDH was enzymatically active in metacestode vesicle extracts. The compounds disulfiram, myricetin, quercetin, sanguinarine, and seven quinazoline carboxamides were evaluated for their ability to inhibit recombinantly expressed EmTDH. The most potent inhibitors, albeit not very strong or highly specific, were disulfiram, myricetin and sanguinarine. These compounds were subsequently tested for activity against E. multilocularis metacestode vesicles and primary parasite cells and only sanguinarine demonstrated significant in vitro activity. However, TDH is not its only cellular target, and it is also known to be highly toxic. Our findings suggest that additional targets of sanguinarine should be explored, and that it may serve as a foundation for developing more specific compounds against the parasite. Moreover, the EmTDH assay could be a valuable high-throughput, target-based platform for discovering novel anti-echinococcal compounds.
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Affiliation(s)
- Marc Kaethner
- Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
| | - Pascal Zumstein
- Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland
| | - Joachim Müller
- Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
| | - Matías Preza
- Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
| | - Philipp Grossenbacher
- Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
| | - Anissa Bartetzko
- Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
| | - Laura Vetter
- Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
| | - Martin Lochner
- Institute of Biochemistry and Molecular Medicine, University of Bern, Bern, Switzerland
| | - Stefan Schürch
- Department of Chemistry, Biochemistry and Pharmaceutical Sciences, University of Bern, Bern, Switzerland
| | - Clement Regnault
- Integrated Protein Analysis - Mass Spectrometry Unit, MVLS Shared Research Facilities, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom
| | | | - Britta Lundström-Stadelmann
- Institute of Parasitology, Vetsuisse Faculty, University of Bern, Bern, Switzerland; Multidisciplinary Center for Infectious Diseases, University of Bern, Bern, Switzerland.
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Mihai CM, Lupu A, Chisnoiu T, Balasa AL, Baciu G, Lupu VV, Popovici V, Suciu F, Enache FD, Cambrea SC, Stoicescu RM. A Comprehensive Analysis of Echinococcus granulosus Infections in Children and Adolescents: Results of a 7-Year Retrospective Study and Literature Review. Pathogens 2025; 14:53. [PMID: 39861014 PMCID: PMC11768134 DOI: 10.3390/pathogens14010053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 12/29/2024] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Cystic echinococcosis (CE) is a neglected tropical parasitic disease linked with significant social and economic burdens worldwide. The scientific community has minimal information on echinococcosis in Romanian people, and hospital medical records are the only sources that may be used to investigate its status. A 7-year retrospective clinical study on pediatric patients with CE from Southeast Romania was performed, and 39 children and adolescents were included, aged 2-15 years old. They were hospitalized with cystic echinococcosis in the Pediatric Department and Pediatric Surgery Department of Constanta County Clinical Emergency Hospital "St. Apostle Andrew" between 1 January 2017 and 1 October 2024. Twenty-nine (74.36%) pediatric patients came from rural zones, and 10 (25.64%) had urban residences. In total, 28 children (71.79%) had contact with four different animals (dogs, goats, pigs, and sheep); only four were from urban zones, and they had contact only with dogs. Data regarding the length of hospital stay, cyst location, and complications were collected and analyzed. According to the medical files, the diagnosis was established using imaging techniques and serological tests for CE. IgE and IgG reported appreciable variations in correlation with all parameters, and significant differences (p < 0.05) were recorded. IgE levels considerably increased in cases of no animal contact, pulmonary involvement, complications, surgical treatment, and multiple hospitalizations. Moderate IgE values were recorded in cases of urban residences, pig and sheep contact, and hepatic involvement. The IgG concentration considerably increased with sheep contact and moderately increased in cases of rural zones, hepatic involvement, complications, and surgical treatment. The results show that incidental discovery, symptoms, complications, multiple dissemination, pulmonary involvement, and dog and pig contact increase the hospitalization time. Extensive data analysis supports our results. Our findings highlight the complexity of managing E. granulosus infections in children and evidence the importance of a multidisciplinary approach, combining early diagnostic tools, tailored medical therapy, and careful surgical intervention when necessary.
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Affiliation(s)
- Cristina Maria Mihai
- Department of Pediatrics, Faculty of General Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania; (C.M.M.); (A.L.B.)
- Pediatrics, County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Ancuta Lupu
- Department of Pediatrics, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.L.); (V.V.L.)
| | - Tatiana Chisnoiu
- Department of Pediatrics, Faculty of General Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania; (C.M.M.); (A.L.B.)
- Pediatrics, County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Adriana Luminita Balasa
- Department of Pediatrics, Faculty of General Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania; (C.M.M.); (A.L.B.)
- Pediatrics, County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Ginel Baciu
- Department of Pediatrics, Faculty of Medicine and Pharmacy, “Dunărea de Jos” University of Galati, 800008 Galati, Romania;
| | - Vasile Valeriu Lupu
- Department of Pediatrics, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania; (A.L.); (V.V.L.)
| | - Violeta Popovici
- Center for Mountain Economics, “Costin C. Kritescu” National Institute of Economic Research (INCE-CEMONT), Romanian Academy, 725700 Vatra-Dornei, Romania
| | - Felicia Suciu
- Department of Analysis and Quality Control of Drugs, Faculty of Pharmacy, “Ovidius” University of Constanta, Str. Căpitan Aviator Al. Șerbănescu, nr.6, Campus Corp C, 900470 Constanta, Romania;
| | - Florin-Daniel Enache
- Department of Pediatric Surgery and Orthopedics, Faculty of General Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania;
- Pediatric Surgery, County Clinical Emergency Hospital of Constanta, 900591 Constanta, Romania
| | - Simona Claudia Cambrea
- Department of Infectious Diseases, Faculty of General Medicine, “Ovidius” University of Constanta, 900470 Constanta, Romania;
| | - Ramona Mihaela Stoicescu
- Department of Microbiology and Immunology, Faculty of Pharmacy, “Ovidius” University of Constanta, Str. Căpitan Aviator Al. Șerbănescu, nr.6, Campus Corp C, 900470 Constanta, Romania;
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Sato K, Hikosaka N, Kouguchi H, Irie T, Morimatsu M, Agui T. Narrowing the region of candidate genes that control the development of protoscoleces of Echinococcus multilocularis in the mouse liver. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2025; 127:105704. [PMID: 39657901 DOI: 10.1016/j.meegid.2024.105704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 12/05/2024] [Accepted: 12/06/2024] [Indexed: 12/12/2024]
Abstract
Alveolar echinococcosis is a zoonosis caused by the larval stage of Echinococcus multilocularis. In previous studies, QTL analysis using C57BL/6 N (B6) and DBA/2 (D2) which differ in susceptibility suggested the presence of genes on chromosome 1 that control protoscolex development. In this study, we constructed several congenic mice with different chromosome 1 regions substituted to confirm the presence of responsible genes and to narrow down the regions where the responsible genes exist. Five lines of third-generation congenic strain were constructed and infection experiments were conducted. The results showed that the development of protoscolex was seen in the two lines, resulting to narrow-down the responsible region between 69.4 cM and 70.67 cM. There were 18 genes having different SNPs and 10 genes having amino acid substitutions between B6 and D2 within this region. Infection experiments with third-generation of congenic mice succeeded in narrowing down the chromosomal region determining protoscolex development, resulting to reduce the number of candidate genes. The identification of the gene responsible for protoscolex development will contribute to the control of E. multilocularis infection.
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Affiliation(s)
- Keisuke Sato
- Laboratory of Laboratory Animal Science and Medicine, Department of Applied Veterinary Sciences, Graduate School of Veterinary Medicine, N18 W9, Kita-Ku, Sapporo, Hokkaido 060-0819, Japan.
| | - Naritaka Hikosaka
- Laboratory of Laboratory Animal Science and Medicine, Department of Applied Veterinary Sciences, Graduate School of Veterinary Medicine, N18 W9, Kita-Ku, Sapporo, Hokkaido 060-0819, Japan
| | - Hirokazu Kouguchi
- Department of Infectious Diseases, Hokkaido Institute of Public Health, N19 W12, Kita-Ku, Sapporo, Hokkaido 060-0819, Japan
| | - Takao Irie
- Department of Infectious Diseases, Hokkaido Institute of Public Health, N19 W12, Kita-Ku, Sapporo, Hokkaido 060-0819, Japan
| | - Masami Morimatsu
- Laboratory of Laboratory Animal Science and Medicine, Department of Applied Veterinary Sciences, Graduate School of Veterinary Medicine, N18 W9, Kita-Ku, Sapporo, Hokkaido 060-0819, Japan
| | - Takashi Agui
- Laboratory of Laboratory Animal Science and Medicine, Department of Applied Veterinary Sciences, Graduate School of Veterinary Medicine, N18 W9, Kita-Ku, Sapporo, Hokkaido 060-0819, Japan
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11
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Faizi F, Mahjub R, Torabi N, Motavallihaghi S, Fallah M. Cationized albumin conjugated solid lipid nanoparticles as vectors for delivery of albendazole against cystic echinococcosis. Parasit Vectors 2024; 17:542. [PMID: 39731191 DOI: 10.1186/s13071-024-06473-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2024] [Accepted: 09/03/2024] [Indexed: 12/29/2024] Open
Abstract
BACKGROUND Cystic echinococcosis (CE) is a common neglected parasitic disease. Nanoparticles containing drugs have been widely utilized in various formulations for several purposes, including improving the bioavailability of drugs by increasing the solubility and dissolution rate of the nanoparticles. The purpose of this study was to evaluate the effects of solid lipid nanoparticles containing albendazole and conjugated to albumin (B-SLN + ABZ) as a novel treatment approach for hydatid cysts in vivo. METHODS Albendazole-loaded solid lipid nanoparticles were prepared by emulsification and solvent evaporation method. The experimental mice were assessed for prophylactic and therapeutic effects of the drugs. Ultrastructural changes were observed by transmission electron microscopy. RESULTS The variance analysis of the fitted model indicated that the Glyceryl monostearate (GMS)/soy lecithin concentration ratio and the amount of albendazole had a significant effect on nanoparticle size. The GMS/soy lecithin concentration ratio and the amount of albendazole had a notable effect on nanoparticle polydispersity index (PdI) and entrapment efficiency (EE%), respectively. During chemoprophylaxis, the B-SLN + ABZ group showed a lower number and weight of cysts (0.90 ± 0.73 and 15.01 ± 10.46, respectively) compared with the ABZ + SLN group (1.4 ± 0.51 and 26.73 ± 9.92, respectively). In addition, therapeutic efficacy analysis showed a significant reduction in wet weights of metacestodes in mice treated with both B-SLN + ABZ (29.37 ± 13.82 mg) and SLN + ABZ (35.88 ± 7.49 mg) compared with the control group (59.78 ± 3.80 mg). CONCLUSIONS The results showed that B-SLN + ABZ nanoparticles were more effective against E. granulosus cysts compared with free ABZ. The cysts in the animals receiving B-SLN + ABZ every 24 h showed more ultrastructural changes.
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Affiliation(s)
- Fariba Faizi
- Department of Medical Parasitology and Mycology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Reza Mahjub
- Faculty of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Negin Torabi
- Department of Parasitology and Mycology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Seyedmousa Motavallihaghi
- Department of Medical Parasitology and Mycology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Mohammad Fallah
- Department of Medical Parasitology and Mycology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
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Borhani M, Fathi S, Harandi MF, Casulli A, Ding J, Liu M, Zhang W, Wen H. Echinococcus granulosus sensu lato control measures: a specific focus on vaccines for both definitive and intermediate hosts. Parasit Vectors 2024; 17:533. [PMID: 39716337 DOI: 10.1186/s13071-024-06581-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Accepted: 11/11/2024] [Indexed: 12/25/2024] Open
Abstract
Echinococcosis, a neglected zoonotic disease caused by Echinococcus tapeworms, presents significant public health challenges worldwide. Cystic and alveolar echinococcosis has substantial health and economic impacts, necessitating effective prevention and control strategies. The present review provides a framework to expand our knowledge regarding key components of echinococcosis prevention and control, including phases, options, targets and available tools as well as current gaps and challenges in the field. Furthermore, we discuss the progress made in developing vaccines for the intermediate and definitive hosts and review the limitations and obstacles in vaccine development for definitive hosts. Abundant information is available on various aspects of the Echinococcus vaccine in sheep. Livestock vaccination effectively reduces Echinococcus transmission to sheep, offering a feasible control measure in intermediate hosts. However, vaccine development for the definitive host, i.e. dogs, exhibits significant challenges. Information gaps regarding the immune-mediated protective responses in dogs, repeatability of results, factors influencing the immune response, reinfection resistance, potential age-related decreases in worm burden and factors associated with the antifecundity effect are key challenges that should be addressed in canine vaccine development, and research collaboration, innovative technologies, and a deeper understanding of transmission dynamics are crucial. Multisectoral coordination under the One Health framework, with long-term political commitment and national and international cooperation, is critical for effective control in endemic areas.
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Affiliation(s)
- Mehdi Borhani
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, 130062, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China
| | - Saeid Fathi
- Department of Parasite Vaccine Research and Production, Razi Vaccine and Serum Research Institute, Karaj, Iran
| | - Majid Fasihi Harandi
- Research Center for Hydatid Disease in Iran, Kerman University of Medical Sciences, Kerman, Iran
| | - Adriano Casulli
- WHO Collaborating Centre for the Epidemiology, Detection and Control of Cystic and Alveolar Echinococcosis, Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
- European Union Reference Laboratory for Parasites (EURLP), Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
| | - Jing Ding
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, 130062, China
| | - Mingyuan Liu
- State Key Laboratory for Zoonotic Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
| | - Wenbao Zhang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China
| | - Hao Wen
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, China.
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Qin M, Yang G, Yan J, Wang L, Feng Y, Wang D, Wang Q, Hou Y, Zhao J, Lei J, Wang Z, Jiang M, Yu C, Gavotte L, Frutos R. Assessment of compliance and therapeutic efficacy of albendazole treatment in Chinese patients with echinococcosis. Infect Dis Poverty 2024; 13:98. [PMID: 39707489 DOI: 10.1186/s40249-024-01268-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 12/04/2024] [Indexed: 12/23/2024] Open
Abstract
BACKGROUND Echinococcosis is an infectious parasitic disease that is extremely harmful to human health. Albendazole is provided free of charge to patients requiring medication under the central government finance transfer payment scheme for echinococcosis control and prevention in China. Our aim is to monitor the state of patient medication and its therapeutic impact, which will help improve medication compliance and the therapeutic effect. METHODS Random cluster sampling was used to select 10 echinococcosis-endemic counties in China, and all albendazole-treated patients in these counties were investigated. The chi-square and Kruskal-Wallis tests were used to compare two or more rates or constituent ratios, and multiple logistic regression analysis was used to identify the influencing factors. The records of patients were reviewed to obtain the initial diagnosis results as well as the most recent follow-up results and time, and efficacy was assessed. RESULTS We examined 899 patient files treated with albendazole in 10 endemic counties. Of the 582 evaluable files, 7.9% did not take albendazole, and 69.2% did not take albendazole regularly. Only 22.9% took albendazole regularly. Of the 536 patients who took albendazole, 242 exhibited adverse reactions. Patients who were Tibetan, herdsmen, received no formal education, used emulsion, and exhibited adverse reactions demonstrated poor compliance. A total of 174 patients with cystic echinococcosis received their most recent imaging follow-up results within one year of the investigation date. Among them, 9 patients met the criteria for cure, accounting for 5.2%; 56 patients showed effectiveness, accounting for 32.2%; 105 patients were deemed ineffective, accounting for 59.8%; 5 patients experienced recurrence, accounting for 2.9%. CONCLUSIONS Albendazole medication compliance in patients with echinococcosis is not ideal. We must prioritize health education and promotion for Tibetans, herdsmen, and those without formal education. Patients who adhered to their medication regimen achieved higher rates of cure and effectiveness. To improve medication compliance and efficacy, it is particularly important to improve communication and medication guidance for patients receiving emulsions and those with adverse reactions after taking albendazole. Simultaneously strengthen patients' attention to follow-up and re-examination.
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Affiliation(s)
- Min Qin
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Centre for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology; WHO Collaborating Centre for Tropical Diseases, National Centre for International Research On Tropical Diseases, Shanghai, China
- Chaoyang District Center for Diseases Prevention and Control of Beijing, Beijing, China
| | - Guobing Yang
- Gansu Provincial Center for Disease Control and Prevention, Lanzhou, China
| | - Jun Yan
- Chinese Centre for Disease Control and Prevention, Beijing, China.
| | - Liying Wang
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Centre for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology; WHO Collaborating Centre for Tropical Diseases, National Centre for International Research On Tropical Diseases, Shanghai, China.
| | - Yu Feng
- Gansu Provincial Center for Disease Control and Prevention, Lanzhou, China
| | - Dong Wang
- Gansu Provincial Center for Disease Control and Prevention, Lanzhou, China
| | - Qian Wang
- Sichuan Provincial Center for Disease Control and Prevention, Chengdu, China
| | - Yanyan Hou
- Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention, Urumqi, China
| | - Jiangshan Zhao
- Xinjiang Uygur Autonomous Region Center for Disease Control and Prevention, Urumqi, China
| | - Jiaxi Lei
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Centre for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology; WHO Collaborating Centre for Tropical Diseases, National Centre for International Research On Tropical Diseases, Shanghai, China
| | - Zhiyi Wang
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Centre for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology; WHO Collaborating Centre for Tropical Diseases, National Centre for International Research On Tropical Diseases, Shanghai, China
| | - Mingzhe Jiang
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Centre for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology; WHO Collaborating Centre for Tropical Diseases, National Centre for International Research On Tropical Diseases, Shanghai, China
| | - Chenghang Yu
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Centre for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology; WHO Collaborating Centre for Tropical Diseases, National Centre for International Research On Tropical Diseases, Shanghai, China
| | - Laurent Gavotte
- Espace-Dev, UMR 228, Université de Montpellier, Montpellier, France
| | - Roger Frutos
- Centre de Cooperation International en Recherche Agronomique Pour Le Développement, UMR 17, Intertryp, Campus International de Baillarguet, Montpellier, France
- Faculty of Medicine-Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
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Zhu Y, He Y, Yin Z, Chen N, Qi X, Ding J, Li Y, Zhang F. Enhanced Immune Response Against Echinococcus Granulosus Through a CTLA-4/B7 Affinity-Based Vaccine. Vaccines (Basel) 2024; 12:1440. [PMID: 39772100 PMCID: PMC11680267 DOI: 10.3390/vaccines12121440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2024] [Revised: 12/17/2024] [Accepted: 12/17/2024] [Indexed: 01/11/2025] Open
Abstract
Background: Echinococcosis is a zoonotic infectious disease that poses a significant threat to the health of individuals living in rural regions. While vaccination represents a potential strategy for disease prevention, there is currently no effective vaccine available for humans to prevent cystic echinococcosis (CE). This study aimed to design a novel multi-epitope vaccine (MEV) against Echinococcus granulosus for human use, employing immunoinformatics methods. Methods: We identified core epitopes from two key antigens, EgA31 and EgG1Y162, and integrated them into the immunoglobulin variable region of CTLA-4 (CTLA-4lgV) to create the CVE31-162 vaccine construct. The secondary and tertiary structures of the CVE31-162 were established using bioinformatics methods. The interaction between the CVE31-162 and B7 molecules was assessed through molecular dynamics simulations. Finally, both in vitro and in vivo experiments were conducted to validate the effectiveness of the CVE31-162 against the immunological effects of Echinococcus granulosus. Results: Bioinformatics analysis indicated that CVE31-162 exhibits favorable antigenicity, stability, and non-allergenicity. Furthermore, CVE31-162 demonstrated a stable three-dimensional structural model. Molecular docking (MD) and molecular dynamics simulations (MDS) revealed a strong binding affinity between CVE31-162 and B7 molecules. Immune simulation results suggested that the vaccine elicits robust humoral and cell-mediated immune responses. Both in vitro and in vivo experiments demonstrated that immunized mice exhibited significantly elevated levels of antigen-specific antibodies and enhanced lymphocyte proliferation compared to the control group. Conclusions:CVE31-162, which is based on the interaction between CTLA-4 and B7, represents a promising multi-epitope vaccine for Echinococcus granulosus.
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Affiliation(s)
- Yuejie Zhu
- Reproductive Medicine Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China;
| | - Yueyue He
- Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China; (Y.H.); (Z.Y.); (J.D.)
| | - Ziyue Yin
- Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China; (Y.H.); (Z.Y.); (J.D.)
- School of Public Health, Guilin Medical University, Guilin 541100, China
| | - Na Chen
- Clinical Laboratory Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; (N.C.); (X.Q.)
| | - Xingxing Qi
- Clinical Laboratory Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; (N.C.); (X.Q.)
| | - Jianbing Ding
- Department of Immunology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi 830011, China; (Y.H.); (Z.Y.); (J.D.)
- State Key Laboratory of Pathogenesis, Prevention, Treatment of Central Asian High Incidence Diseases, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China
| | - Yujiao Li
- Post-Doctoral Research Station of the Clinical Medicine, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China
| | - Fengbo Zhang
- Clinical Laboratory Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China; (N.C.); (X.Q.)
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Lissandrin R, Cicerone O, Vola A, D'Alessandro G, Frassini S, Manciulli T, Famularo S, De Silvestri A, Viganò J, Quaretti P, Ansaloni L, Brunetti E, Maestri M. Machine learning to predict the decision to perform surgery in hepatic echinococcosis. HPB (Oxford) 2024:S1365-182X(24)02462-6. [PMID: 39755481 DOI: 10.1016/j.hpb.2024.12.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/17/2024] [Accepted: 12/17/2024] [Indexed: 01/06/2025]
Abstract
BACKGROUND Cystic echinococcosis (CE) is a significant public health issue, primarily affecting the liver. While several management strategies exist, there is a lack of predictive tools to guide surgical decisions for hepatic CE. This study aimed to develop predictive models to support surgical decision-making in hepatic CE, enhancing the precision of patient allocation to surgical or non-surgical management pathways. METHODS This retrospective analysis included 406 hepatic CE patients treated at our center (2009-2021). Clinical, imaging, and treatment data were used to develop a Cox regression and a decision tree model to identify factors influencing surgical intervention, with model performance validated using K-fold cross-validation, train/test split, bootstrapping. RESULTS Imaging findings and symptomatology emerged as the most significant predictors. The Cox model demonstrated a concordance index of 0.94 and an AUC of 0.96, while the decision tree model identified imaging, cyst stage, and symptoms as critical factors, achieving strong performance across validation techniques (mean AUC 0.950; 95% CI: [0.889, 0.978]). CONCLUSION This study presents validated predictive models for assessing surgical risk in hepatic CE. Integrating these models into clinical practice offers a dynamic tool that surpasses static guidelines, optimizing patient allocation to surgical or non-surgical pathways and potentially improving outcomes.
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Affiliation(s)
| | - Ottavia Cicerone
- University of Pavia, Dipartimento di Scienze Clinico-chirurgiche, Diagnostiche e Pediatriche, Italy
| | - Ambra Vola
- Microbiology and Virology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Simone Frassini
- University of Pavia, Dipartimento di Scienze Clinico-chirurgiche, Diagnostiche e Pediatriche, Italy
| | - Tommaso Manciulli
- University of Florence, Department of Experimental and Clinical Medicine, Florence, Italy
| | - Simone Famularo
- Hepatobiliary Surgery Unit, Fondazione Policlinico Universitario A. Gemelli, IRCCS, Catholic University of the Sacred Heart, Rome, Italy
| | - Annalisa De Silvestri
- SSD Biostatistica E Clinical Trial Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | - Jacopo Viganò
- Fondazione IRCCS Policlinico San Matteo, SC Chirurgia Generale 1, Pavia, Italy
| | - Pietro Quaretti
- Fondazione IRCCS Policlinico San Matteo, SS Radiologia Interventistica, Pavia, Italy
| | - Luca Ansaloni
- Fondazione IRCCS Policlinico San Matteo, SC Chirurgia Generale 1, Pavia, Italy
| | - Enrico Brunetti
- Fondazione IRCCS Policlinico San Matteo, SC Malattie Infettive, Pavia, Italy
| | - Marcello Maestri
- Fondazione IRCCS Policlinico San Matteo, SC Chirurgia Generale 1, Pavia, Italy.
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Robers S, Reinehr M, Haibach L, Furrer E, Cincera A, Kronenberg PA, Eichenberger RM, Deplazes P, Deibel A, Müllhaupt B, Weber A. Histopathological assessment of the viability of hepatic alveolar echinococcosis. Histopathology 2024; 85:857-867. [PMID: 39044671 DOI: 10.1111/his.15280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 06/25/2024] [Accepted: 06/30/2024] [Indexed: 07/25/2024]
Abstract
AIMS Infections by the larval stage of the tape worms Echinococcus multilocularis and Echinococcus granulosus s.l. are potentially fatal zoonoses affecting humans as dead-end hosts. Histopathological evaluation of hepatic echinococcosis is an integral part of patient management, including the distinction between alveolar (AE) and cystic echinococcosis (CE), which are associated with different disease courses and treatments. To improve histopathological assessment of Echinococcus lesions, we aimed to develop robust criteria to evaluate their viability and decay. METHODS AND RESULTS Histomorphological criteria for determining parasitic viability based on the morphology of parasite structures and different stages of their decay were defined based on a clinically and molecularly defined cohort comprising 138 specimens from 112 patients (59 AE and 53 CE); 618 AE lesions were assessed for histopathological viability comparing haematoxylin and eosin (H&E) staining with mAbEm18 and mAbEm2G11 immunostaining. Moreover, parasite viability was systematically mapped in cross-sections of five additional AE lesions. Protoscoleces in CE and AE displayed variable states of degeneration. Albendazole had no significant effect on the morphology of parasite structures. Viability assessment revealed high agreement between H&E and mAbEm18, but not mAbEm2G11 staining, suggesting mAbEm18 staining as reliable for parasite viability assessment. H&E and mAbEm18 staining displayed a central-peripheral gradient of parasite viability and decay across parasitic lesions, with decayed cystic lesions located more towards the lesion centre while the most viable cystic lesions were located more peripherally. CONCLUSIONS Histopathological criteria corroborated by mAbEm18 staining provide a simple and reliable tool to assess the viability of AE lesions, knowledge of which is a valuable decision-making tool for further treatment.
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Affiliation(s)
- Selina Robers
- Department of Pathology and Molecular Pathology, University of Zurich (UZH) and University Hospital Zurich (USZ), Zurich, Switzerland
| | - Michael Reinehr
- Department of Pathology and Molecular Pathology, University of Zurich (UZH) and University Hospital Zurich (USZ), Zurich, Switzerland
| | - Lillemor Haibach
- Epidemiology, Biostatistics and Prevention Institute, Zurich, Switzerland
| | - Eva Furrer
- Epidemiology, Biostatistics and Prevention Institute, Zurich, Switzerland
| | - Annina Cincera
- Epidemiology, Biostatistics and Prevention Institute, Zurich, Switzerland
| | - Philipp Andreas Kronenberg
- Vetsuisse and Medical Faculty, Institute of Parasitology, University of Zurich, Zurich, Switzerland
- Medical Micro- and Molecular Biology, Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences, Zurich University of Applied Sciences (ZHAW), Wädenswil, Switzerland
| | - Ramon Marc Eichenberger
- Vetsuisse and Medical Faculty, Institute of Parasitology, University of Zurich, Zurich, Switzerland
- Medical Micro- and Molecular Biology, Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences, Zurich University of Applied Sciences (ZHAW), Wädenswil, Switzerland
| | - Peter Deplazes
- Vetsuisse and Medical Faculty, Institute of Parasitology, University of Zurich, Zurich, Switzerland
- Department of Hepatology and Gastroenterology, University of Zurich and University Hospital Zurich, Zurich, Switzerland
| | - Ansgar Deibel
- Department of Hepatology and Gastroenterology, University of Zurich and University Hospital Zurich, Zurich, Switzerland
| | - Beat Müllhaupt
- Department of Hepatology and Gastroenterology, University of Zurich and University Hospital Zurich, Zurich, Switzerland
| | - Achim Weber
- Department of Pathology and Molecular Pathology, University of Zurich (UZH) and University Hospital Zurich (USZ), Zurich, Switzerland
- Institute of Molecular Cancer Research, University of Zurich (UZH), Zurich, Switzerland
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17
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Carbonara M, Buono F, Morea A, Sgroi G, Maurelli MP, Locantore F, Trerotoli P, Indraccolo F, Stufano A, Schino V, D'Alessio N, Veneziano V, Lovreglio P, Otranto D, Iatta R. Echinococcus granulosus complex infection in wild boar hunters and auxiliary hunting dogs. One Health 2024; 19:100908. [PMID: 39430231 PMCID: PMC11490901 DOI: 10.1016/j.onehlt.2024.100908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 09/27/2024] [Accepted: 10/02/2024] [Indexed: 10/22/2024] Open
Abstract
Cystic echinococcosis (CE) caused by Echinococcus granulosus sensu lato (s.l.) is a zoonotic neglected tropical disease endemic in Italy, which perpetuates in several intermediate hosts, including wild boars, and dogs as definitive hosts. People living in rural and livestock-raising areas are exposed to E. granulosus s.l. infection, as well as people leading outdoor activities in endemic regions. Therefore, this study was designed to assess the exposure to Echinococcus spp. in wild boar hunters, the role of their hunting dogs as parasite reservoirs, along with hunter's knowledge on the infection risk. From December 2022 to May 2023, wild boar hunters (n = 122) from southern Italy were recruited on volunteer basis for blood and serum sampling and a questionnaire enquiring socio-demographic, anamnestic data and knowledge on CE was also filled out. Sera were tested for Echinococcus spp. IgG by a commercial enzyme-linked immunosorbent assay (Euroimmun ELISA®, Germany). In addition, faecal samples from their hunting dogs (n = 208) were screened for Taeniidae eggs by parasitological and molecular approaches. Overall, six (4.9 %) hunters scored either positive or borderline for IgG anti-Echinococcus spp., of which one presented a calcified hepatic cyst at abdominal ultrasonography. In addition, 6.3 % Taeniidae prevalence was recorded in faecal samples (13/208) of hunting dogs, and E. granulosus sensu stricto (s.s.) was molecularly identified in two samples. The statistical analysis revealed the risk factors (odds ratio > 1, p < 0.05) associated with parasitic exposure, including the hunter geographical provenience, and the presence of animals around or in the house. The E. granulosus s.l. exposure of hunters herein detected, coupled with the parasite molecular positivity of their hunting dogs and the limited awareness on Echinococcus spp. life cycle/infection risk, highlight the relevance to promote health surveillance and educational programs within the hunting category, for minimizing the cestode circulation in the wildlife-urban premises.
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Affiliation(s)
| | - Francesco Buono
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, Italy
| | - Anna Morea
- Interdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Giovanni Sgroi
- Department of Animal Health, Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Italy
| | - Maria Paola Maurelli
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, Italy
| | | | - Paolo Trerotoli
- Interdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Francesca Indraccolo
- Interdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Angela Stufano
- Interdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Valentina Schino
- Interdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Nicola D'Alessio
- Department of Animal Health, Istituto Zooprofilattico Sperimentale del Mezzogiorno, Portici, Italy
| | - Vincenzo Veneziano
- Department of Veterinary Medicine and Animal Production, University of Naples Federico II, Naples, Italy
| | - Piero Lovreglio
- Interdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Domenico Otranto
- Department of Veterinary Medicine, University of Bari Aldo Moro, Italy
- Department of Veterinary Clinical Sciences, City University of Hong Kong, SAR, China
| | - Roberta Iatta
- Interdisciplinary Department of Medicine, University of Bari Aldo Moro, Bari, Italy
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18
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Jiang N, Chen Y, Li T, Sun Y, Su Y, Wang Y, Shen Y, Cao J. Proteomic analysis of mouse liver lesions at all three stages of Echinococcus granulosus infection. PLoS Negl Trop Dis 2024; 18:e0012659. [PMID: 39625960 PMCID: PMC11614251 DOI: 10.1371/journal.pntd.0012659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 10/25/2024] [Indexed: 12/06/2024] Open
Abstract
Echinococcus granulosus, a zoonotic parasite, can severely damage host health or even lead to host death. In humans, early diagnosis of E. granulosus infection is difficult because the initial stages of the infection tend to be asymptomatic, this delays treatment and worsens prognosis in most patients. Herein, we present a comprehensive, temporal proteomic atlas of the liver at three stages of E. granulosus infection and analyze the changes in the proteome of host focal lesions; this atlas may provide an overview of the effects of E. granulosus in the host, as well as the interactions between them. We identified 3,197 proteins from mice model at 1, 3, and 6 months after E. granulosus infection; of these proteins, 760 were differentially expressed (520 upregulated; 240 downregulated). Moreover, 228 differentially expressed proteins were screened through cluster analysis and classified into four clusters according to their changing trends. Subsequently, candidate molecules related to cyst invasion, growth, candidate pathways and proteins related to angiogenesis were noted to demonstrate important value in mouse liver. Next, we used western blotting to verify the presence of the aforementioned proteins in mouse liver. In the later stages, E. granulosus infection was noted to result in significant enrichment of crucial proteins facilitating protoscoleces growth and development and inhibition of amino acid and lipid metabolic enzyme expression in mouse liver; it was also noted to transform host metabolism by weakening oxidative phosphorylation and enhancing glycolysis. In conclusion, we explored the molecular mechanisms underlying the parasitic processes of E. granulosus through proteomic analysis. Our results provide evidence that may enable the exploration of core regulatory targets for early and effective diagnosis and immunotherapy of E. granulosus infection, as well as parasite-host interactions involved in cystic echinococcosis development.
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Affiliation(s)
- Nan Jiang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Parasitic Diseases at Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai, China
- Key Laboratory of Parasite and Vector Biology, National Health Commission of the People’s Republic of China, Shanghai, China
- World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China
- The School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yang Chen
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Parasitic Diseases at Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai, China
- State Key Laboratory of Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang, China
| | - Teng Li
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Parasitic Diseases at Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai, China
- Key Laboratory of Parasite and Vector Biology, National Health Commission of the People’s Republic of China, Shanghai, China
- World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China
| | - Yeting Sun
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Parasitic Diseases at Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai, China
- Key Laboratory of Parasite and Vector Biology, National Health Commission of the People’s Republic of China, Shanghai, China
- World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China
| | - Yaxin Su
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Parasitic Diseases at Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai, China
- Key Laboratory of Parasite and Vector Biology, National Health Commission of the People’s Republic of China, Shanghai, China
- World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China
| | - Ying Wang
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Parasitic Diseases at Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai, China
- Key Laboratory of Parasite and Vector Biology, National Health Commission of the People’s Republic of China, Shanghai, China
- World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China
| | - Yujuan Shen
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Parasitic Diseases at Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai, China
- Key Laboratory of Parasite and Vector Biology, National Health Commission of the People’s Republic of China, Shanghai, China
- World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China
| | - Jianping Cao
- National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute of Parasitic Diseases at Chinese Center for Disease Control and Prevention, Chinese Center for Tropical Diseases Research, Shanghai, China
- Key Laboratory of Parasite and Vector Biology, National Health Commission of the People’s Republic of China, Shanghai, China
- World Health Organization Collaborating Centre for Tropical Diseases, Shanghai, China
- The School of Global Health, Chinese Center for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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19
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Sorouri N, Soleymani N, Sadr S, Rahdar A, Ebrahimzadeh E, Borji H. Investigating the therapeutic effects of curcumin nanocapsules in hydatid cyst-infected mice. Exp Parasitol 2024; 267:108860. [PMID: 39528001 DOI: 10.1016/j.exppara.2024.108860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2024] [Revised: 10/29/2024] [Accepted: 11/07/2024] [Indexed: 11/16/2024]
Abstract
BACKGROUND/OBJECTIVE The primary treatment for cysts is surgery, including removing the cyst and administering the appropriate chemical drugs. Herbal remedies have gained popularity as a viable and secure alternative to conventional pharmaceuticals. It may be advantageous to use nanocapsules to overcome the bioavailability challenges associated with herbal remedies like curcumin. The present study aims to provide insights into the effectiveness of curcumin nanocapsules in treating hydatid infections. METHODS Curcumin-loaded oil-in-water surfactant-based biocompatible nanomicelles were developed from dissolving Curcumin in 1% (w/w) solutions of ethyl butyrate oil by dissolving an amount of fatty acid sodium caprylate (SC, 0.09 g) and F127 (0.009 g), phosphate-buffered saline (PBS at pH 7.4) under vigorous stirring at a fixed ethyl butyrate-to-surfactant molar ratio of 10 and final total volume of 50 mL. The excess of free PHT was eliminated by dialysis for 24 h. Following five months after infection, 45 mice were divided into six groups. Groups 1, 2, and 3 were treated daily with curcumin nanocapsules (0.5, 0.25, 0.125 mg/ml) for one month. Group 4 was treated with curcumin (0.5 mg/ml), group 5 was treated with albendazole (150 mg/kg), and group 6 was the negative control group without treatments (only received saline). A detailed analysis of the cysts' physical characteristics, including their size and weight, has been conducted. RESULTS The mean zeta potential spectrum of the nanocapsules was -33.96 mV. Regarding the total cyst numbers, all three nanocapsule groups had significantly lower total cyst numbers than the curcumin, albendazole, and negative control groups. Regarding the total cyst weight, all three nanocapsule groups had a significantly lower total cyst weight than the curcumin and negative control groups. Regarding the cyst with the maximum size, nanocapsules groups 1 and 2 had a significantly smaller size than the curcumin, albendazole, and negative control groups. CONCLUSION The current study found that encapsulation positively affects curcumin efficacy as a superior alternative to chemical drugs, offering both biological advantages and environmental benefits.
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Affiliation(s)
- Negar Sorouri
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
| | - Nooshinmehr Soleymani
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
| | - Soheil Sadr
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
| | - Abbas Rahdar
- Department of Physics, University of Zabol, Zabol, Iran.
| | - Elahe Ebrahimzadeh
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
| | - Hassan Borji
- Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran.
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20
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Nezhad NZ, Nezhad HZ, Shahpar A, Shahrebabak AG, Shahrebabak MG, Farokhi FR. From mammary mystery to parasitic surprise: a rare case of primary breast hydatid cyst. BMC Infect Dis 2024; 24:1369. [PMID: 39614184 DOI: 10.1186/s12879-024-10270-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Accepted: 11/25/2024] [Indexed: 12/01/2024] Open
Abstract
BACKGROUND Primary breast hydatid cyst is an exceedingly rare manifestation of echinococcosis, with an incidence of less than 0.27% among all hydatid cyst cases. CASE REPORT This report presents a unique case of a 51-year-old multiparous female who initially presented with a painless left breast mass. Initial imaging studies, including ultrasonography and mammography, revealed a 4.5 × 4 cm cyst classified as BI-RADS 3. The cyst was initially managed with fine-needle aspiration and conservative treatment. However, it recurred twice over a six-month period, necessitating surgical excision. Preoperative laboratory work ups revealed eosinophilia, a finding initially overlooked but later recognized as significant. Histopathological examination of the excised specimen confirmed the diagnosis of a hydatid cyst. Post-surgical management included albendazole therapy, regular imaging follow-ups, and patient education on hygiene practices to prevent reinfection. CONCLUSION This case highlights the importance of considering parasitic etiologies in the differential diagnosis of breast masses, particularly in endemic regions. It also underscores the value of a multidisciplinary approach in managing such rare cases. The unexpected diagnosis of a primary breast hydatid cyst in this case serves as a reminder of the diverse presentations of echinococcosis and the need for heightened clinical suspicion in atypical breast lesions. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Nazanin Zeinali Nezhad
- Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
| | | | - Amirhossein Shahpar
- Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman, Iran
| | - Aazam Gholami Shahrebabak
- Department of Pediatrics Afzalipour Hospital, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Maryam Gholami Shahrebabak
- Department of Pediatrics, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
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21
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Li Y, Tang Y, He Y, Zhou Z. Neck echinococcosis: A case report. Asian J Surg 2024:S1015-9584(24)02536-3. [PMID: 39580284 DOI: 10.1016/j.asjsur.2024.10.202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 10/21/2024] [Accepted: 10/31/2024] [Indexed: 11/25/2024] Open
Affiliation(s)
- Yushan Li
- Department of Ultrasound Medicine, Gansu Provincial People's Hospital, Lanzhou, Gansu Province, 730000, China
| | - Yuling Tang
- First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, 730000, China; Department of Ultrasound Medicine, Gansu Provincial People's Hospital, Lanzhou, Gansu Province, 730000, China
| | - Yizhong He
- First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, 730000, China; Department of Ultrasound Medicine, Gansu Provincial People's Hospital, Lanzhou, Gansu Province, 730000, China
| | - Zubang Zhou
- Department of Ultrasound Medicine, Gansu Provincial People's Hospital, Lanzhou, Gansu Province, 730000, China; First School of Clinical Medical, Gansu University of Chinese Medicine, Lanzhou, Gansu Province, 730000, China.
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22
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Tenzin C, Dendup T, Torgerson PR, Deplazes P, Zangmo S, Wangmo C, Tsheten T, Zangpo T. The burden and distribution of cystic echinococcosis in Bhutan: a retrospective study. Parasitology 2024:1-9. [PMID: 39511989 DOI: 10.1017/s0031182024001069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
Cystic echinococcosis (CE), caused by Echinococcus granulosus s.l. is a neglected zoonosis posing a significant public health challenge. Little is known about human CE in Bhutan. This study was conducted to gain an understanding of the burden, distribution, and potential risk factors of CE in Bhutan. From January 2015 to December 2019 data from Jigme Dorji Wangchuck National Referral Hospital (JDWNRH) and 6 other district-level hospitals were reviewed. Descriptive statistics were used to summarize the data. DALYs and Poisson regression models were used to estimate the burden and explore the relationship between cases and possible risk factors. A total of 159 cases were recorded. Most cases (145) were admitted to the surgical ward and 14 cases were referred to India. The average annual incidence was 4.4 cases per 100 000 population. The burden of disease was estimated to be approximately 39 DALYs per year for treatment-seeking cases, or possibly 80 DALYs per year including non-treatment seeking cases. This translates to approximately to 5.2 DALYs and 10.2 per 100 000 per year respectively. The commonest sites of infection were the liver (78%) and lungs (13%). Most cases were treated with surgery (>82%), and more than 47% were admitted to the hospital for >4 days. Policy interventions targeting community engagement, awareness, education, high risk occupational groups, females, and those living in the endemic districts of the central and western regions may yield larger gains. More studies and the institution of a surveillance system can help better guide policy interventions.
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Affiliation(s)
| | - Tashi Dendup
- Save the Children International, Bhutan Country Office, Chang Geydaphu, Thimphu, Bhutan
| | - P R Torgerson
- Section of Veterinary Epidemiology, Vetsuisse Faculty, Winterthurerstrasse, Zurich, Switzerland
| | - Peter Deplazes
- Institute of Parasitology, Medical and Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Sonam Zangmo
- Department of Internal Medicine, Jigme Dorji Wangchuck National Referral Hospital, Thimphu, Bhutan
| | | | - Tsheten Tsheten
- National Center for Epidemiology and Population Health, College of Health and Medicine, Australian National University, Canberra, Australia
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Wang W, Li J, Qi W, Chen Y, Tian M, Wu C, Zhang Y, Yu Y, Han S, Han X, Duan L, Zhang W. Drug repurposing for hard-to-treat human alveolar echinococcosis: pyronaridine and beyond. Parasitology 2024:1-8. [PMID: 39508157 DOI: 10.1017/s0031182024001124] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2024]
Abstract
Human alveolar echinococcosis is a hard-to-treat and largely untreated parasitic disease with high associated health care costs. The current antiparasitic treatment for alveolar echinococcosis relies exclusively on albendazole, which does not act parasiticidally and can induce severe adverse effects. Alternative, and most importantly, improved treatment options are urgently required. A drug repurposing strategy identified the approved antimalarial pyronaridine as a promising candidate against Echinococcus multilocularis infections. Following a 30-day oral regimen (80 mg kg−1 day−1), pyronaridine achieved an excellent therapeutic outcome in a clinically relevant hepatic alveolar echinococcosis murine model, showing a significant reduction in both metacestode size (72.0%) and counts (85.2%) compared to unmedicated infected mice, which revealed significantly more potent anti-echinococcal potency than albendazole treatment at an equal dose (metacestode size: 42.3%; counts: 4.1%). The strong parasiticidal activity of pyronaridine was further confirmed by the destructive damage to metacestode tissues observed morphologically. In addition, a screening campaign combined with computational similarity searching against an approved drug library led to the identification of pirenzepine, a gastric acid-inhibiting drug, exhibiting potent parasiticidal activity against protoscoleces and in vitro cultured small cysts, which warranted further in vivo investigation as a promising anti-echinococcal lead compound. Pyronaridine has a known drug profile and a long track record of safety, and its repurposing could translate rapidly to clinical use for human patients with alveolar echinococcosis as an alternative or salvage treatment.
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Affiliation(s)
- Weisi Wang
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, China
- NHC Key Laboratory of Parasite and Vector Biology, Shanghai, China
- WHO Collaborating Centre for Tropical Diseases, Shanghai, China
- National Center for International Research on Tropical Diseases, Shanghai, China
| | - Jun Li
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Wenjing Qi
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
- Basic Medical College, Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Ying Chen
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, China
- NHC Key Laboratory of Parasite and Vector Biology, Shanghai, China
- WHO Collaborating Centre for Tropical Diseases, Shanghai, China
- National Center for International Research on Tropical Diseases, Shanghai, China
| | - Mengxiao Tian
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
- Basic Medical College, Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Chuanchuan Wu
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
- Basic Medical College, Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Yao Zhang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Yingfang Yu
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, China
- NHC Key Laboratory of Parasite and Vector Biology, Shanghai, China
- WHO Collaborating Centre for Tropical Diseases, Shanghai, China
- National Center for International Research on Tropical Diseases, Shanghai, China
| | - Shuai Han
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, China
- NHC Key Laboratory of Parasite and Vector Biology, Shanghai, China
- WHO Collaborating Centre for Tropical Diseases, Shanghai, China
- National Center for International Research on Tropical Diseases, Shanghai, China
| | - Xiumin Han
- Qinghai Provincial People's Hospital, Xining, Qinghai, China
| | - Liping Duan
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), Shanghai, China
- NHC Key Laboratory of Parasite and Vector Biology, Shanghai, China
- WHO Collaborating Centre for Tropical Diseases, Shanghai, China
- National Center for International Research on Tropical Diseases, Shanghai, China
| | - Wenbao Zhang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
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24
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Sun T, Yang Y, Qiu Y, Wang T, Yang M, Shen S, Wang W. High PD-1 and CTLA-4 expression correlates with host immune suppression in patients and a mouse model infected with Echinococcus multilocularis. Parasit Vectors 2024; 17:437. [PMID: 39456030 PMCID: PMC11515268 DOI: 10.1186/s13071-024-06511-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 09/26/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND Alveolar echinococcosis (AE), a fatal disease caused by Echinococcus multilocularis, often affects the liver, with tumor-like growth. However, the mechanism by which E. multilocularis evades host immune surveillance remains unclear. METHODS We collected liver specimens from hepatic alveolar echinococcosis (HAE) patients and established a mouse model of E. multilocularis infection. Immunofluorescence staining and flow cytometry were performed to analyze programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) expression in human samples, while flow cytometry and quantitative real-time polymerase chain reaction (PCR) were performed for similar analyses in mouse samples. Cell proliferation and protoscolex (PSC) killing assays were designed to explore how E. multilocularis induces host immunosuppression. RESULTS An inflammatory reaction band with high PD-1 and CTLA-4 expression was found in close liver tissue (CLT). The ratio of regulatory T cells (Tregs) was higher in CLT than in distant liver tissue (DLT), and Tregs in CLT tended to express higher levels of PD-1 and CTLA-4 than those in DLT from HAE patients. Echinococcus multilocularis-infected mice showed significantly elevated expression of PD-1 and CTLA-4 on splenocytes and peritoneal cells. PD-1/PD-L1 or CTLA-4 pathway blockade could relieve the immunosuppressive effects of Tregs from infected mice and enhance PSC killing by mouse splenocytes. CONCLUSIONS E. multilocularis regulated the function of T cells via the PD-1/PD-L1- and CTLA-4-dependent pathways and subsequently evaded host immune attacks. These findings provide insights for investigating the pathogenic mechanism of AE.
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Affiliation(s)
- Ting Sun
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Yi Yang
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Yiwen Qiu
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Tao Wang
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Ming Yang
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Shu Shen
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China
| | - Wentao Wang
- Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
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Loos JA, Negro PS, Ortega HH, Salinas FJ, Arán M, Pellizza L, Salerno GL, Cumino AC. Anti-echinococcal effect of metformin in advanced experimental cystic echinococcosis: reprogrammed intermediary carbon metabolism in the parasite. Antimicrob Agents Chemother 2024; 68:e0094124. [PMID: 39264188 PMCID: PMC11459915 DOI: 10.1128/aac.00941-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 08/09/2024] [Indexed: 09/13/2024] Open
Abstract
Metformin, a safe biguanide derivative with antiproliferative properties, has shown antiparasitic efficacy against the Echinococcus larval stage. Hence, we assessed the efficacy of a dose of 250 mg kg-1 day-1 in experimental models of advanced CE, at 6 and 12 months post-infection with oral and intraperitoneal administration, respectively. At this high dose, metformin reached intracystic concentrations between 0.7 and 1.7 mM and triggered Eg-TOR inhibition through AMPK activation by AMP-independent and -dependent mechanisms, which are dependent on drug dose. Cystic metformin uptake was controlled by increased expression of organic cation transporters in the presence of the drug. In both experimental models, metformin reduced the weight of parasite cysts, altered the ultrastructural integrity of their germinal layers, and reduced the intracystic availability of glucose, limiting the cellular carbon and energy charge and the proliferative capacity of metacestodes. This glucose depletion in the parasite was associated with a slight increase in cystic uptake of 2-deoxiglucose and the transcriptional induction of GLUT genes in metacestodes. In this context, drastic glycogen consumption led to increased lactate production and altered intermediary metabolism in treated metacestodes. Specifically, the fraction of reducing soluble sugars decreased twofold, and the levels of non-reducing soluble sugars, such as sucrose and trehalose, were modified in both cystic fluid and germinal cells. Taken together, our findings highlight the relevance of metformin as a promising candidate for CE treatment and warrant further research to improve the therapeutic conditions of this chronic zoonosis in humans.
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Affiliation(s)
- Julia A. Loos
- IIPROSAM, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Mar del Plata, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mar del Plata, Argentina
| | - Perla S. Negro
- Parasitología y Enfermedades Parasitarias, Facultad de Ciencias Veterinarias, Universidad Nacional de Rosario, Casilda, Santa Fe, Argentina
| | - Hugo H. Ortega
- Centro de Medicina Comparada, ICiVet-Litoral, Universidad Nacional del Litoral-CONICET, Esperanza, Santa Fe, Argentina
| | - Facundo J. Salinas
- Centro de Medicina Comparada, ICiVet-Litoral, Universidad Nacional del Litoral-CONICET, Esperanza, Santa Fe, Argentina
| | - Martín Arán
- Fundación Instituto Leloir e Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA)—CONICET, Buenos Aires, Argentina
| | - Leonardo Pellizza
- Fundación Instituto Leloir e Instituto de Investigaciones Bioquímicas de Buenos Aires (IIBBA)—CONICET, Buenos Aires, Argentina
| | - Graciela L. Salerno
- Fundación Para Investigaciones Biológicas Aplicadas (FIBA), Mar del Plata, Argentina
| | - Andrea C. Cumino
- IIPROSAM, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Mar del Plata, Argentina
- Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Mar del Plata, Argentina
- Departamento de Química, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata (UNMdP), Mar del Plata, Argentina
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Aydin S, Irgul B, Memis KB, Kızılgoz V, Kantarci M. Characteristics of the imaging diagnosis of alveolar echinococcosis. World J Gastrointest Surg 2024; 16:2748-2754. [PMID: 39351560 PMCID: PMC11438814 DOI: 10.4240/wjgs.v16.i9.2748] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 06/06/2024] [Accepted: 06/24/2024] [Indexed: 09/18/2024] Open
Abstract
Alveolar echinococcosis (AE) primarily manifests in the liver and exhibits characteristics resembling those of slow-growing malignant tumours. Untreated Echinococcus multilocularis infection can be lethal. By infiltrating the vascular systems, biliary tracts, and the hilum of the liver, it might lead to various problems. Due to its ability to infiltrate neighbouring tissues or metastasize to distant organs, AE can often be mistaken for malignancies. We present a concise overview of the epidemiological and pathophysiological characteristics of AE, as well as the clinical manifestations of the disease. This article primarily examines the imaging characteristics of AE using various imaging techniques such as ultrasonography, computed tomography (CT), magnetic resonance imaging, diffusion-weighted imaging, and virtual non-enhanced dual-energy CT. We additionally examined the contribution of radiography in the diagnosis, treatment, and monitoring of the condition.
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Affiliation(s)
- Sonay Aydin
- Department of Radiology, Erzincan Binali Yıldırım University, Faculty of Medicine, Erzincan 24100, Türkiye
| | - Baris Irgul
- Department of Radiology, Erzincan Binali Yıldırım University, Faculty of Medicine, Erzincan 24100, Türkiye
| | - Kemal Bugra Memis
- Department of Radiology, Erzincan Binali Yıldırım University, Faculty of Medicine, Erzincan 24100, Türkiye
| | - Volkan Kızılgoz
- Department of Radiology, Erzincan Binali Yıldırım University, Faculty of Medicine, Erzincan 24100, Türkiye
| | - Mecit Kantarci
- Department of Radiology, Erzurum Ataturk University, Erzurum 25000, Türkiye
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Wang N, Xian J, Zhao P, Zhao W, Pu N, Jia X, Zhang Y, Bo X, Wang Z. Evaluation of protective immune responses induced by DNA vaccines encoding Echinococcus granulosus EgM123 protein in Beagle dogs. Front Vet Sci 2024; 11:1444741. [PMID: 39386253 PMCID: PMC11462624 DOI: 10.3389/fvets.2024.1444741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 09/09/2024] [Indexed: 10/12/2024] Open
Abstract
Introduction Echinococcus granulosus, known as cystic echinococcosis, is a prominent zoonotic parasitic disease of significant global concern. The definitive hosts serves as the primary reservoir for the transmission of echinococcosis, as well as a main factor in the prevention and control of the disease. Unfortunately, there is currently no commercially available vaccine for these hosts. Nevertheless, DNA vaccines show potential as a feasible strategy for the control and management of parasitic diseases. Methods In this study, the EgM123 antigen was selected for its well-documented immunogenic properties to develop a DNA vaccine aimed at combating E. granulosus infection in canines. Results The results showed a marked increase in IgG levels in the group vaccinated with pVAX1-EgM123 DNA compared to the PBS group. Additionally, the cytokines IL-1, IFN-γ, IL-4, and IL-6 were significantly upregulated in the pVAX1-EgM123 DNA vaccine group. Furthermore, in comparison to the PBS control group, the EgM123 DNA vaccine group exhibited a notable 87.85% reduction in worm burden and a 65.00% inhibition in segment development. Discussion These findings indicate that the pVAX1-EgM123 DNA vaccine shows promising immunogenicity, successfully eliciting a targeted immune response in canines. Moreover, it significantly diminishes the worm burden and hinders the progression of tapeworms in the pVAX1-EgM123 DNA vaccine group. These findings suggest that the pVAX1-EgM123 DNA vaccine holds promise as a potential candidate vaccine for combating E. granulosus infection in dogs.
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Affiliation(s)
- Ning Wang
- State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Shihezi, China
- Institute of Animal Husbandry and Veterinary Medicine, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, China
- College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Jinwen Xian
- State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Shihezi, China
- Institute of Animal Husbandry and Veterinary Medicine, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, China
- College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Pengpeng Zhao
- State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Shihezi, China
- Institute of Animal Husbandry and Veterinary Medicine, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, China
- College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Wenqing Zhao
- State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Shihezi, China
- Institute of Animal Husbandry and Veterinary Medicine, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, China
- College of Animal Science and Technology, Tarim University, Xinjiang, China
| | - Na Pu
- State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Shihezi, China
- Institute of Animal Husbandry and Veterinary Medicine, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, China
- College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Xinyue Jia
- State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Shihezi, China
- Institute of Animal Husbandry and Veterinary Medicine, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, China
- College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Yanyan Zhang
- State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Shihezi, China
| | - Xinwen Bo
- State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Shihezi, China
- Institute of Animal Husbandry and Veterinary Medicine, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, China
- College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Zhengrong Wang
- State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Shihezi, China
- Institute of Animal Husbandry and Veterinary Medicine, Xinjiang Academy of Agricultural and Reclamation Science, Shihezi, China
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Berg T, Aehling NF, Bruns T, Welker MW, Weismüller T, Trebicka J, Tacke F, Strnad P, Sterneck M, Settmacher U, Seehofer D, Schott E, Schnitzbauer AA, Schmidt HH, Schlitt HJ, Pratschke J, Pascher A, Neumann U, Manekeller S, Lammert F, Klein I, Kirchner G, Guba M, Glanemann M, Engelmann C, Canbay AE, Braun F, Berg CP, Bechstein WO, Becker T, Trautwein C. S2k-Leitlinie Lebertransplantation der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) und der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2024; 62:1397-1573. [PMID: 39250961 DOI: 10.1055/a-2255-7246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/11/2024]
Affiliation(s)
- Thomas Berg
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Niklas F Aehling
- Bereich Hepatologie, Medizinischen Klinik II, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Tony Bruns
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martin-Walter Welker
- Medizinische Klinik I Gastroent., Hepat., Pneum., Endokrin. Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Tobias Weismüller
- Klinik für Innere Medizin - Gastroenterologie und Hepatologie, Vivantes Humboldt-Klinikum, Berlin, Deutschland
| | - Jonel Trebicka
- Medizinische Klinik B für Gastroenterologie und Hepatologie, Universitätsklinikum Münster, Münster, Deutschland
| | - Frank Tacke
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Pavel Strnad
- Medizinische Klinik III, Universitätsklinikum Aachen, Aachen, Deutschland
| | - Martina Sterneck
- Medizinische Klinik und Poliklinik I, Universitätsklinikum Hamburg, Hamburg, Deutschland
| | - Utz Settmacher
- Klinik für Allgemein-, Viszeral- und Gefäßchirurgie, Universitätsklinikum Jena, Jena, Deutschland
| | - Daniel Seehofer
- Klinik für Viszeral-, Transplantations-, Thorax- und Gefäßchirurgie, Universitätsklinikum Leipzig, Leipzig, Deutschland
| | - Eckart Schott
- Klinik für Innere Medizin II - Gastroenterologie, Hepatologie und Diabetolgie, Helios Klinikum Emil von Behring, Berlin, Deutschland
| | | | - Hartmut H Schmidt
- Klinik für Gastroenterologie und Hepatologie, Universitätsklinikum Essen, Essen, Deutschland
| | - Hans J Schlitt
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg, Regensburg, Deutschland
| | - Johann Pratschke
- Chirurgische Klinik, Charité Campus Virchow-Klinikum - Universitätsmedizin Berlin, Berlin, Deutschland
| | - Andreas Pascher
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Münster, Münster, Deutschland
| | - Ulf Neumann
- Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Universitätsklinikum Essen, Essen, Deutschland
| | - Steffen Manekeller
- Klinik und Poliklinik für Allgemein-, Viszeral-, Thorax- und Gefäßchirurgie, Universitätsklinikum Bonn, Bonn, Deutschland
| | - Frank Lammert
- Medizinische Hochschule Hannover (MHH), Hannover, Deutschland
| | - Ingo Klein
- Chirurgische Klinik I, Universitätsklinikum Würzburg, Würzburg, Deutschland
| | - Gabriele Kirchner
- Klinik und Poliklinik für Chirurgie, Universitätsklinikum Regensburg und Innere Medizin I, Caritaskrankenhaus St. Josef Regensburg, Regensburg, Deutschland
| | - Markus Guba
- Klinik für Allgemeine, Viszeral-, Transplantations-, Gefäß- und Thoraxchirurgie, Universitätsklinikum München, München, Deutschland
| | - Matthias Glanemann
- Klinik für Allgemeine, Viszeral-, Gefäß- und Kinderchirurgie, Universitätsklinikum des Saarlandes, Homburg, Deutschland
| | - Cornelius Engelmann
- Charité - Universitätsmedizin Berlin, Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum (CVK) und Campus Charité Mitte (CCM), Berlin, Deutschland
| | - Ali E Canbay
- Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum, Bochum, Deutschland
| | - Felix Braun
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
| | - Christoph P Berg
- Innere Medizin I Gastroenterologie, Hepatologie, Infektiologie, Universitätsklinikum Tübingen, Tübingen, Deutschland
| | - Wolf O Bechstein
- Klinik für Allgemein- und Viszeralchirurgie, Universitätsklinikum Frankfurt, Frankfurt, Deutschland
| | - Thomas Becker
- Klinik für Allgemeine Chirurgie, Viszeral-, Thorax-, Transplantations- und Kinderchirurgie, Universitätsklinikum Schlewswig-Holstein, Kiel, Deutschland
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Aledavoud A, Mohammadi M, Ataei A, Shahesmaeilinejad A, Harandi MF. Thyroid involvement in cystic echinococcosis: a systematic review. BMC Infect Dis 2024; 24:889. [PMID: 39210268 PMCID: PMC11363358 DOI: 10.1186/s12879-024-09778-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2024] [Accepted: 08/20/2024] [Indexed: 09/04/2024] Open
Abstract
BACKGROUND Thyroid Hydatid Cyst (THC), a pathological state induced by the larval form of Echinococcus granulosus, represents a multifaceted clinical entity with nonspecific symptoms, making both diagnosis and treatment intricate. The current understanding of THC's attributes is somewhat limited. To gain a broader perspective on the disease's clinical and epidemiological characteristics, we have systematically reviewed the existing literature. METHODS We performed an extensive review of articles on THC across four key scientific databases: PubMed, Scopus, Web of Science, and Google Scholar. Our study encompassed all patients diagnosed with THC through post-surgical pathology or Fine Needle Aspiration Cytology (FNAC) examinations, extracting clinical, epidemiological, and therapeutic data of THC patients from publications up to October 2023. RESULTS From 770 articles, 57 met our criteria, detailing 75 THC patients. The gender ratio was 2.36 females per one male. The patients averaged 36.1 years old, with common symptoms including neck mass, hoarseness, shortness of breath, and dysphagia. The left lobe was involved in most patients, and only 21.3% had extrathyroidal involvement. Cysts averaged 36.4 mm in diameter, with cystic nodules being the most frequent imaging finding (91.2%). Serological tests were performed for 42.6% of cases, of which 62.5% were positive. Surgery was undertaken in 71 patients (94.6%). CONCLUSION Cystic echinococcosis (CE) of the thyroid should be considered as part of the differential diagnosis in patients with cervicofacial mass, especially in endemic countries. The present study provides reliable data to improve our understanding of the features of the disease for a better diagnosis and management.
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Affiliation(s)
- Ali Aledavoud
- Research Center for Hydatid Disease in Iran, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Mohammad Mohammadi
- School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Ali Ataei
- School of Medicine, Bam University of Medical Sciences, Bam, Iran
| | - Armita Shahesmaeilinejad
- HIV/STI Surveillance Research Center, WHO Collaborating Center for HIV Surveillance, Institute for Futures Studies in Health, Kerman University of Medical Sciences, Kerman, Iran
- Institute of Clinical Epidemiology and Biometry, Julius-Maximilians-Universität Würzburg, Würzburg, Germany
| | - Majid Fasihi Harandi
- Research Center for Hydatid Disease in Iran, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
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Tsukanov VV, Vasyutin AV, Tonkikh JL. Parasites of the liver: A global problem? World J Gastroenterol 2024; 30:3554-3559. [PMID: 39193571 PMCID: PMC11346153 DOI: 10.3748/wjg.v30.i30.3554] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 07/12/2024] [Accepted: 07/24/2024] [Indexed: 08/08/2024] Open
Abstract
Parasitic liver diseases can be caused by trematodes, cestodes, nematodes, and protozoa. This pathology is significant because millions of people in different parts of the world have liver parasites, which can manifest themselves in the development of inflammation, liver cysts, cholecystitis, cholelithiasis, pancreatitis and liver cirrhosis that are often threatening their lives. The International Agency for Research on Cancer considers three species of trematodes, Schistosoma haematobium, Opisthorchis viverrini and Clonorchis sinensis, to be carcinogens. Complex modern examination methods, in some cases including extensive screening of large populations, are required for diagnosing liver parasites. Treatment of parasitic liver diseases is differentiated and can involve a combination of surgical and therapeutic measures. There is no doubt that the clinical and epidemiological scale allows one to regard parasitic liver diseases as a global healthcare problem.
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Affiliation(s)
- Vladislav V Tsukanov
- Clinical Department of the Digestive System Pathology of Adults and Children, Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Scientific Research Institute of Medical Problems of the North, Krasnoyarsk 660022, Russia
| | - Alexander V Vasyutin
- Clinical Department of the Digestive System Pathology of Adults and Children, Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Scientific Research Institute of Medical Problems of the North, Krasnoyarsk 660022, Russia
| | - Julia L Tonkikh
- Clinical Department of the Digestive System Pathology of Adults and Children, Federal Research Center “Krasnoyarsk Science Center” of the Siberian Branch of the Russian Academy of Sciences, Scientific Research Institute of Medical Problems of the North, Krasnoyarsk 660022, Russia
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Barnadas-Carceller B, Del Portillo HA, Fernandez-Becerra C. Extracellular vesicles as biomarkers in parasitic disease diagnosis. CURRENT TOPICS IN MEMBRANES 2024; 94:187-223. [PMID: 39370207 DOI: 10.1016/bs.ctm.2024.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/08/2024]
Abstract
Parasitic diseases constitute a major global health problem, affecting millions of people worldwide. Recent advances in the study of extracellular vesicles (EVs) have opened up new strategies for biomarker discovery in protozoan and helminth infections. Analyses of EVs in cultures and biological fluids have identified numerous potential biomarkers that could be useful for early and differential diagnosis, monitoring therapeutic responses, and the overall management and control of these diseases. Despite the potential of these biomarkers, several challenges must be addressed, including limited research, the need for standardized protocols, and the reproducibility of results across studies. In many parasitic infections, EVs have been obtained from various sample types, including plasma from human patients and mouse models, as well as cultures of the parasites at different stages. EVs were isolated by various methods and predominantly characterized through proteomic analysis or RNA sequencing to assess their cargo and identify potential biomarkers. These biomarker candidates were investigated and validated using different assays such as ELISA, Western Blot, and ROC curves. Overall, the use of EVs is considered a promising new diagnostic strategy for parasite infections, but further research with larger cohorts, standardized methods, and additional validation tests are essential for effective diagnosis and management of these diseases.
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Affiliation(s)
- Berta Barnadas-Carceller
- ISGlobal, Barcelona Institute for Global Health, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain; IGTP Institut d'Investigació Germans Trias I Pujol, Badalona, Barcelona, Spain
| | - Hernando A Del Portillo
- ISGlobal, Barcelona Institute for Global Health, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain; IGTP Institut d'Investigació Germans Trias I Pujol, Badalona, Barcelona, Spain; ICREA, Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain
| | - Carmen Fernandez-Becerra
- ISGlobal, Barcelona Institute for Global Health, Facultat de Medicina i Ciències de la Salut, Universitat de Barcelona (UB), Barcelona, Spain; IGTP Institut d'Investigació Germans Trias I Pujol, Badalona, Barcelona, Spain; CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Instituto de Salud Carlos III, Madrid, Spain.
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Nijiati M, Tuerdi M, Damola M, Yimit Y, Yang J, Abulaiti A, Mutailifu A, Aihait D, Wang Y, Zou X. A deep learning radiomics model based on CT images for predicting the biological activity of hepatic cystic echinococcosis. Front Physiol 2024; 15:1426468. [PMID: 39175611 PMCID: PMC11338923 DOI: 10.3389/fphys.2024.1426468] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 07/15/2024] [Indexed: 08/24/2024] Open
Abstract
Introduction: Hepatic cystic echinococcosis (HCE) is a widely seen parasitic infection. Biological activity is crucial for treatment planning. This work aims to explore the potential applications of a deep learning radiomics (DLR) model, based on CT images, in predicting the biological activity grading of hepatic cystic echinococcosis. Methods: A retrospective analysis of 160 patients with hepatic echinococcosis was performed (127 and 33 in training and validation sets). Volume of interests (VOIs) were drawn, and radiomics features and deep neural network features were extracted. Feature selection was performed on the training set, and radiomics score (Rad Score) and deep learning score (Deep Score) were calculated. Seven diagnostics models (based on logistic regression algorithm) for the biological activity grading were constructed using the selected radiomics features and two deep model features respectively. All models were evaluated using the receiver operating characteristic curve, and the area under the curve (AUC) was calculated. A nomogram was constructed using the combined model, and its calibration, discriminatory ability, and clinical utility were assessed. Results: 12, 6 and 10 optimal radiomics features, deep learning features were selected from two deep learning network (DLN) features, respectively. For biological activity grading of hepatic cystic echinococcosis, the combined model demonstrated strong diagnostic performance, with an AUC value of 0.888 (95% CI: 0.837-0.936) in the training set and 0.876 (0.761-0.964) in the validation set. The clinical decision analysis curve indicated promising results, while the calibration curve revealed that the nomogram's prediction result was highly compatible with the actual result. Conclusion: The DLR model can be used for predicting the biological activity grading of hepatic echinococcosis.
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Affiliation(s)
- Mayidili Nijiati
- Department of Radiology, The Fourth Affiliated Hospital of Xinjiang Medical UniversityÜrümqi, Xinjiang, China
- Department Xinjiang Key Laboratory of Artificial Intelligence Assisted Imaging Diagnosis, Kashi, China
| | - Mireayi Tuerdi
- Department of Infectious Diseases, The First People’s Hospital of Kashi Prefecture, Kashi, China
| | - Maihemitijiang Damola
- Department of Radiology, The First People’s Hospital of Kashi Prefecture, Kashi, China
| | - Yasen Yimit
- Department Xinjiang Key Laboratory of Artificial Intelligence Assisted Imaging Diagnosis, Kashi, China
- Department of Radiology, The First People’s Hospital of Kashi Prefecture, Kashi, China
| | - Jing Yang
- Huiying Medical Imaging Technology, The Fourth Affiliated Hospital of Xinjiang Medical University, Beijing, China
| | - Adilijiang Abulaiti
- Department of Radiology, The First People’s Hospital of Kashi Prefecture, Kashi, China
| | | | - Diliaremu Aihait
- Department of Radiology, The First People’s Hospital of Kashi Prefecture, Kashi, China
| | - Yunling Wang
- Department of Imaging Center, The First Affiliated Hospital of Xinjiang Medical University, Ürümqi, China
| | - Xiaoguang Zou
- Department Xinjiang Key Laboratory of Artificial Intelligence Assisted Imaging Diagnosis, Kashi, China
- Clinical Medical Research Center, The First People’s Hospital of Kashi Prefecture, Kashi, China
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Gao H, Bianba Z, Mo X, Hu W, Feng Z, Zhou F, Zhang T. Receptor Tyrosine Kinase Signaling Involves Echinococcus-Host Intercommunication: A Potential Therapeutic Target in Hepatic Echinococcosis. Trop Med Infect Dis 2024; 9:175. [PMID: 39195613 PMCID: PMC11360685 DOI: 10.3390/tropicalmed9080175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 08/02/2024] [Accepted: 08/05/2024] [Indexed: 08/29/2024] Open
Abstract
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.
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Affiliation(s)
- Haijun Gao
- Chengdu Fifth People’s Hospital (Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine; The Second Clinical Medical College), Chengdu 611130, China;
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases; National Health Commission Key Laboratory of Parasite and Vector Biology; WHO Collaborating Center for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai 200025, China; (X.M.); (W.H.); (Z.F.)
| | - Zhuoma Bianba
- National Health Commission Key Laboratory of Echinococcosis Prevention and Control, Xizang Center for Disease Control and Prevention, Lhasa 850000, China;
| | - Xiaojin Mo
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases; National Health Commission Key Laboratory of Parasite and Vector Biology; WHO Collaborating Center for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai 200025, China; (X.M.); (W.H.); (Z.F.)
- National Health Commission Key Laboratory of Echinococcosis Prevention and Control, Xizang Center for Disease Control and Prevention, Lhasa 850000, China;
| | - Wei Hu
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases; National Health Commission Key Laboratory of Parasite and Vector Biology; WHO Collaborating Center for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai 200025, China; (X.M.); (W.H.); (Z.F.)
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot 010070, China
| | - Zheng Feng
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases; National Health Commission Key Laboratory of Parasite and Vector Biology; WHO Collaborating Center for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai 200025, China; (X.M.); (W.H.); (Z.F.)
| | - Fangye Zhou
- Chengdu Fifth People’s Hospital (Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine; The Second Clinical Medical College), Chengdu 611130, China;
| | - Ting Zhang
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases; National Health Commission Key Laboratory of Parasite and Vector Biology; WHO Collaborating Center for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai 200025, China; (X.M.); (W.H.); (Z.F.)
- National Health Commission Key Laboratory of Echinococcosis Prevention and Control, Xizang Center for Disease Control and Prevention, Lhasa 850000, China;
- State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Sciences, Inner Mongolia University, Hohhot 010070, China
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Shen Z, Wang Y, Chen X, Chou S, Wang G, Wang Y, Xu X, Liu J, Wang R. Clinical value of the semi-quantitative parameters of 18F-fluorodeoxyglucose PET/CT in the classification of hepatic echinococcosis in the Qinghai Tibetan area of China. BMC Med Imaging 2024; 24:194. [PMID: 39085759 PMCID: PMC11289940 DOI: 10.1186/s12880-024-01371-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 07/18/2024] [Indexed: 08/02/2024] Open
Abstract
BACKGROUND To investigate the value of 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) semi-quantitative parameters, including the lesion diameter, maximum standardized uptake value (SUVmax), maximum standardized uptake value corrected for lean body mass (SULmax), metabolic lesion volume (MLV), and total lesion glycolysis (TLG), for classifying hepatic echinococcosis. METHODS In total, 20 patients with 36 hepatic echinococcosis lesions were included in the study. Overall, these lesions were categorized as hepatic cystic echinococcosis (HCE) or hepatic alveolar echinococcosis (HAE) according to the pathological results. Multiple semi-parameters including the maximum diameter, SUVmax, SULmax, MLV, and TLG were measured to classify HCE and HAE compared with the pathological results. The receiver operator characteristic curve and area under the curve (AUC) of each quantitative parameter were calculated. The Mann-Whitney U test was used to compare data between the two groups. RESULTS In total, 12 cystic lesions and 24 alveolar lesions were identified after surgery. There were significant differences in SUV max, SUL max, MLV, and TLG between the HAE and HCE groups (Z = - 4.70, - 4.77, - 3.36, and - 4.23, respectively, all P < 0.05). There was no significant difference in the maximum lesion diameter between the two groups (Z = - 0.77, P > 0.05). The best cutoffs of SUV max, SUL max, MLV, and TLG for the differential diagnosis of HAE and HCE were 2.09, 2.67, 27.12, and 18.79, respectively. The AUCs of the four parameters were 0.99, 0.99, 0.85, and 0.94, respectively. The sensitivities were 91.7%, 87.5%, 66.7%, and 85.6%, respectively, and the specificities were 90.1%, 91.7%, 83.3%, and 90.9%, respectively. CONCLUSION 18F-FDG PET/CT semi-quantitative parameters had significant clinical value in the diagnosis and pathological classification of hepatic echinococcosis and evaluation of clinical treatment.
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Affiliation(s)
- Zhihui Shen
- Department of Nuclear Medicine, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China
| | - Yuan Wang
- Department of Nuclear Medicine, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China
| | - Xin Chen
- Department of Pathology, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China
| | - Sai Chou
- Department of General Surgery, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China
| | - Guanyun Wang
- Department of Nuclear Medicine, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China
| | - Yong Wang
- Department of Nuclear Medicine, The Fifth Medical Center, Chinese PLA General Hospital, No. 8, Dongdajie Street, Fengtai District, Beijing, 100071, China
| | - Xiaodan Xu
- Department of Nuclear Medicine, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China
| | - Jiajin Liu
- Department of Nuclear Medicine, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China
| | - Ruimin Wang
- Department of Nuclear Medicine, The First Medical Centre, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
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Rosa DD, Figueredo E, Rosas M, Goñi F. Follow up study of symptomatic human cystic echinococcosis treatment with albendazole and praziquantel, in Uruguay. BMC Infect Dis 2024; 24:737. [PMID: 39060987 PMCID: PMC11282602 DOI: 10.1186/s12879-024-09539-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2023] [Accepted: 06/19/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Cystic echinococcosis (CE) is a chronic disease considered a neglected one. Cystic echinococcosis is endemic in Uruguay and the region. Surgery, using various technical approaches, has the potential to safely remove the cyst(s) and lead to a complete cure in a high number of patients with simple forms of CE. However, surgery may be impractical in patients with multiple cysts in several organs, high surgical risk, or in patients with previous multiple surgeries. In these cases, the pharmacological treatment with the benzimidazolic drug Albendazole (ABZ) alone or combined with Praziquantel (PZQ), has been promising as the best choice to achieve improvement or cure. METHODS In this study, we analyze the results obtained on the anti-parasitic treatment of 43 patients diagnosed with CE between the years 2003 and 2020. Patients were treated before and/or after surgery with ABZ or the combination ABZ/PZQ. The standardize protocol of the anti-parasitic drug treatment before surgery was 7 days, 15 days or 1 month depending on the urgency and availability of the surgical procedure. All cases that involved confirmed locations on lungs underwent immediate surgery with minimal pre-treatment when possible. After surgery, the standardize protocol of anti-parasitic drug treatment consisted of six cycles of 30 days each and resting intervals of 15 days in between. ABZ was used in all cases, administered orally, twice daily, at a total dosage of 15 mg/kg/day, with food high in fat content for improved absorption. The follow up was carried out according to WHO-IWGE guidelines for 5 years. RESULTS Of the 43 patients fourteen were ≤ 15 years of age and had a differentiated pre-surgical treatment. From the ≥ 16 years of age, 36 completed the treatments and the 5 years follow up. Four patients changed geographical locations, without a forwarding contact, after the post-surgery treatment. No patient died during the study. Of the 36 patients that completed the study, 32 were treated only with ABZ; 93.75% achieved treatment success as determined by improvement or cure, and 6.25% treatment failure determined by no change or worsening. The last four patients received the ABZ/PZQ combination therapy and achieved 100% treatment success. CONCLUSION The pharmacological treatment resulted in a good option not only as palliative but also as potentially curative. The main relevance of its use was in cases with previous multiple surgeries or surgeries with potential life-threatening complications due to the number and location of cysts and concurrent comorbidities. A follow-up of at least 5 years would be recommended to assure remission and control of the transmission. More randomized trials are needed to provide clear clinical evidence of different pharmacological treatments for CE.
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Affiliation(s)
- Daniel Da Rosa
- Departament of Parasitology and Mycology, Instituto de Higiene, Facultad de Medicina, Universidad de la República - UDELAR, Montevideo, Uruguay.
| | - Elisa Figueredo
- Departament of Parasitology and Mycology, Instituto de Higiene, Facultad de Medicina, Universidad de la República - UDELAR, Montevideo, Uruguay
| | - Michel Rosas
- Departament of Parasitology and Mycology, Instituto de Higiene, Facultad de Medicina, Universidad de la República - UDELAR, Montevideo, Uruguay
| | - Fernando Goñi
- Department of Neurology, New York University Grossman School of Medicine, New York, USA
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Bold B, Schindler C, Narankhuu U, Shagj A, Bavuujav E, Sodov S, Nyamdorj T, Zinsstag J. The Diagnostic Challenge of Cystic Echinococcosis in Humans: First Assessment of Underreporting Rates in Mongolia. Trop Med Infect Dis 2024; 9:163. [PMID: 39058205 PMCID: PMC11281321 DOI: 10.3390/tropicalmed9070163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 07/12/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024] Open
Abstract
Cystic echinococcosis (CE), caused by the larval stage of Echinococcus granulosus, is significantly underreported in Mongolia due to geographical remoteness, a lack of early diagnostics, and poor clinical management. This study aimed to provide a more accurate estimate of CE in Mongolia by comparing data from surgical (reported) and diagnosed (unreported) cases and assessing the challenges faced by rural doctors in disease management and surveillance. We collected data on surgical cases hospitalized between 2006 and 2016 and newly diagnosed CE cases in 2016 from eight provinces. Using a quasi-Poisson regression model, we extrapolated the collected data to estimate the number of diagnosed cases for the entire country. Additionally, forty health professionals from all 21 provinces rated local clinical management for CE through a questionnaire. The results reveal that surgical cases (2.2 per year) represent only one-eighth of diagnosed cases (15.9 per year). The laboratory facilities, disease reporting, and cyst classification usage scored below 2. These results highlight the significant underreporting of CE in Mongolia and urge human and animal health experts, along with policymakers, to invest in combating CE, particularly in remote provincial areas. This study also emphasizes the need for standard clinical management involving cyst classification according to the WHO-IWGE and seamless integration of CE reporting and monitoring mechanisms, which can significantly contribute to the national and global burden estimation of CE.
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Affiliation(s)
- Bolor Bold
- National Center for Zoonotic Disease, Ulaanbaatar 18131, Mongolia; (U.N.); (A.S.); (T.N.)
- Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland; (C.S.); (J.Z.)
- Department of Public Health, Faculty of Medicine, University of Basel, 4001 Basel, Switzerland
- School of Global Health, Chinese Centre for Tropical Diseases Research, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai 200025, China
| | - Christian Schindler
- Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland; (C.S.); (J.Z.)
- Department of Public Health, Faculty of Medicine, University of Basel, 4001 Basel, Switzerland
| | - Uranshagai Narankhuu
- National Center for Zoonotic Disease, Ulaanbaatar 18131, Mongolia; (U.N.); (A.S.); (T.N.)
| | - Agiimaa Shagj
- National Center for Zoonotic Disease, Ulaanbaatar 18131, Mongolia; (U.N.); (A.S.); (T.N.)
| | - Erdenebileg Bavuujav
- Mongolian Society of Diagnostic Ultrasound, Ulaanbaatar 210648, Mongolia; (E.B.); (S.S.)
| | - Sonin Sodov
- Mongolian Society of Diagnostic Ultrasound, Ulaanbaatar 210648, Mongolia; (E.B.); (S.S.)
| | - Tsogbadrakh Nyamdorj
- National Center for Zoonotic Disease, Ulaanbaatar 18131, Mongolia; (U.N.); (A.S.); (T.N.)
| | - Jakob Zinsstag
- Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland; (C.S.); (J.Z.)
- Department of Public Health, Faculty of Medicine, University of Basel, 4001 Basel, Switzerland
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Kuehn R, Uchiumi LJ, Tamarozzi F. Treatment of uncomplicated hepatic cystic echinococcosis (hydatid disease). Cochrane Database Syst Rev 2024; 7:CD015573. [PMID: 38994714 PMCID: PMC11240857 DOI: 10.1002/14651858.cd015573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/13/2024]
Abstract
BACKGROUND Cystic echinococcosis is a parasitic infection mainly impacting people living in low- and middle-income countries. Infection may lead to cyst development within organs, pain, non-specific symptoms or complications including abscesses and cyst rupture. Treatment can be difficult and varies by country. Treatments include oral medication, percutaneous techniques and surgery. One Cochrane review previously assessed the benefits and harms of percutaneous treatment compared with other treatments. However, evidence for oral medication, percutaneous techniques and surgery in specific cyst stages has not been systematically investigated and the optimal choice remains uncertain. OBJECTIVES To assess the benefits and harms of medication, percutaneous and surgical interventions for treating uncomplicated hepatic cystic echinococcosis. SEARCH METHODS We searched CENTRAL, MEDLINE, two other databases and two trial registries to 4 May 2023. We searched the reference lists of included studies, and contacted experts and researchers in the field for relevant studies. SELECTION CRITERIA We included randomized controlled trials (RCTs) in people with a diagnosis of uncomplicated hepatic cystic echinococcosis of World Health Organization (WHO) cyst stage CE1, CE2, CE3a or CE3b comparing either oral medication (albendazole) to albendazole plus percutaneous interventions, or to surgery plus albendazole. Studies comparing praziquantel plus albendazole to albendazole alone prior to or following an invasive intervention (surgery or percutaneous treatment) were eligible for inclusion. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were symptom improvement, recurrence, inactive cyst at 12 months and all-cause mortality at 30 days. Our secondary outcomes were development of secondary echinococcosis, complications of treatment and duration of hospital stay. We used GRADE to assess the certainty of evidence. MAIN RESULTS We included three RCTs with 180 adults and children with hepatic cystic echinococcosis. Two studies enrolled people aged 5 to 72 years, and one study enrolled children aged 6 to 14 years. One study compared standard catheterization plus albendazole with puncture, aspiration, injection and re-aspiration (PAIR) plus albendazole, and two studies compared laparoscopic surgery plus albendazole with open surgery plus albendazole. The three RCTs were published between 2020 and 2022 and conducted in India, Pakistan and Turkey. There were no other comparisons. Standard catheterization plus albendazole versus PAIR plus albendazole The cyst stages were CE1 and CE3a. The evidence is very uncertain about the effect of standard catheterization plus albendazole compared with PAIR plus albendazole on cyst recurrence (risk ratio (RR) 3.67, 95% confidence interval (CI) 0.16 to 84.66; 1 study, 38 participants; very low-certainty evidence). The evidence is very uncertain about the effects of standard catheterization plus albendazole on 30-day all-cause mortality and development of secondary echinococcosis compared to open surgery plus albendazole. There were no cases of mortality at 30 days or secondary echinococcosis (1 study, 38 participants; very low-certainty evidence). Major complications were reported by cyst and not by participant. Standard catheterization plus albendazole may increase major cyst complications compared with PAIR plus albendazole, but the evidence is very uncertain (RR 10.74, 95% CI 1.39 to 82.67; 1 study, 53 cysts; very low-certainty evidence). Standard catheterization plus albendazole may make little to no difference on minor complications compared with PAIR plus albendazole, but the evidence is very uncertain (RR 1.03, 95% CI 0.60 to 1.77; 1 study, 38 participants; very low-certainty evidence). Standard catheterization plus albendazole may increase the median duration of hospital stay compared with PAIR plus albendazole, but the evidence is very uncertain (4 (range 1 to 52) days versus 1 (range 1 to 15) days; 1 study, 38 participants; very low-certainty evidence). Symptom improvement and inactive cysts at 12 months were not reported. Laparoscopic surgery plus albendazole versus open surgery plus albendazole The cyst stages were CE1, CE2, CE3a and CE3b. The evidence is very uncertain about the effect of laparoscopic surgery plus albendazole on cyst recurrence in participants with CE2 and CE3b cysts compared to open surgery plus albendazole (RR 3.00, 95% CI 0.13 to 71.56; 1 study, 82 participants; very low-certainty evidence). The second study involving 60 participants with CE1, CE2 or CE3a cysts reported no recurrence in either group. The evidence is very uncertain about the effect of laparoscopic surgery plus albendazole on 30-day all-cause mortality in participants with CE1, CE2, CE3a or CE3b cysts compared to open surgery plus albendazole. There was no mortality in either group (2 studies, 142 participants; very low-certainty evidence). The evidence is very uncertain about the effect of laparoscopic surgery plus albendazole on major complications in participants with CE1, CE2, CE3a or CE3b cysts compared to open surgery plus albendazole (RR 0.50, 95% CI 0.13 to 1.92; 2 studies, 142 participants; very low-certainty evidence). Laparoscopic surgery plus albendazole may lead to slightly fewer minor complications in participants with CE1, CE2, CE3a or CE3b cysts compared to open surgery plus albendazole (RR 0.13, 95% CI 0.02 to 0.98; 2 studies, 142 participants; low-certainty evidence). Laparoscopic surgery plus albendazole may reduce the duration of hospital stay compared with open surgery plus albendazole (mean difference (MD) -1.90 days, 95% CI -2.99 to -0.82; 2 studies, 142 participants; low-certainty evidence). Symptom improvement, inactive cyst at 12 months and development of secondary echinococcosis were not reported. AUTHORS' CONCLUSIONS Percutaneous and surgical interventions combined with albendazole can be used to treat uncomplicated hepatic cystic echinococcosis; however, there is a scarcity of randomised evidence directly comparing these interventions. There is very low-certainty evidence to indicate that standard catheterization plus albendazole may lead to fewer cases of recurrence, more major complications and similar complication rates compared to PAIR plus albendazole in adults and children with CE1 and CE3a cysts. There is very low-certainty evidence to indicate that laparoscopic surgery plus albendazole may result in fewer cases of recurrence or fewer major complications compared to open surgery plus albendazole in adults and children with CE1, CE2, CE3a and CE3b cysts. Laparoscopic surgery plus albendazole may lead to slightly fewer minor complications. Firm conclusions cannot be drawn due to the limited number of studies, small sample size and lack of events for some outcomes.
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Affiliation(s)
- Rebecca Kuehn
- Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK
| | - Leonardo J Uchiumi
- Control Program of Cystic Echinococcosis, Ministry of Health, Río Negro Province, Viedma, Argentina
| | - Francesca Tamarozzi
- Department of Infectious Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
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Shang F, Song T, Wang Z, Wu M, Yan C, Wang X. Clinical Application of Artificial Intelligence in the Ultrasound Classification of Hepatic Cystic Echinococcosis. Am J Trop Med Hyg 2024; 111:93-101. [PMID: 38806047 PMCID: PMC11229658 DOI: 10.4269/ajtmh.23-0519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2023] [Accepted: 02/19/2024] [Indexed: 05/30/2024] Open
Abstract
Hepatic cystic echinococcosis (HCE) is a zoonotic disease that occurs when the larvae of Echinococcus granulosus parasitize the livers of humans and mammals. HCE has five subtypes, and accurate subtype classification is critical for choosing a treatment strategy. To evaluate the clinical utility of artificial intelligence (AI) based on convolutional neural networks (CNNs) in the classification of HCE subtypes via ultrasound imaging, we collected ultrasound images from 4,012 HCE patients at the First Affiliated Hospital of Xinjiang Medical University between 2008 and 2020. Specifically, 1,820 HCE images from 967 patients were used as the training and validation sets for the construction of the AI model, and the remaining 6,808 images from 3,045 patients were used as the test set to evaluate the performance of the AI models. The 6,808 images were randomly divided into six groups, and each group contained equal proportions of the five subtypes. The data of each group were analyzed by a resident physician. The accuracy of HCE subtype classification by the AI model and by manual inspection was compared. The AI HCE classification model showed good performance in the diagnosis of subtypes CE1, CE2, CE4, and CE5. The overall accuracy of the AI classification (90.4%) was significantly greater than that of manual classification by physicians (86.1%; P <0.05). The CNN can better identify the five subtypes of HCE on ultrasound images and should help doctors with little experience in more accurately diagnosing HCE.
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Affiliation(s)
- Feng Shang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Ultrasonography Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Tao Song
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Ultrasonography Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Zhengye Wang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, College of Medical Engineering Technology, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Miao Wu
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, College of Medical Engineering Technology, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Chuanbo Yan
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, College of Medical Engineering Technology, Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
| | - Xiaorong Wang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Ultrasonography Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region, China
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Ruze R, Jiang T, Zhang W, Zhang M, Zhang R, Guo Q, Aboduhelili A, Zhayier M, Mahmood A, Yu Z, Ye J, Shao Y, Aji T. Liver autotransplantation and atrial reconstruction on a patient with multiorgan alveolar echinococcosis: a case report. BMC Infect Dis 2024; 24:659. [PMID: 38956482 PMCID: PMC11218102 DOI: 10.1186/s12879-024-09545-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2024] [Accepted: 06/20/2024] [Indexed: 07/04/2024] Open
Abstract
BACKGROUND Alveolar echinococcosis (AE) primarily affects the liver and potentially spreads to other organs. Managing recurrent AE poses significant challenges, especially when it involves critical structures and multiple major organs. CASE PRESENTATION We present a case of a 59-year-old female with recurrent AE affecting the liver, heart, and lungs following two previous hepatectomies, the hepatic lesions persisted, adhering to major veins, and imaging revealed additional diaphragmatic, cardiac, and pulmonary involvement. The ex vivo liver resection and autotransplantation (ELRA), first in human combined with right atrium (RA) reconstruction were performed utilizing cardiopulmonary bypass, and repairs of the pericardium and diaphragm. This approach aimed to offer a potentially curative solution for lesions previously considered inoperable without requiring a donor organ or immunosuppressants. The patient encountered multiple serious complications, including atrial fibrillation, deteriorated liver function, severe pulmonary infection, respiratory failure, and acute kidney injury (AKI). These complications necessitated intensive intraoperative and postoperative care, emphasizing the need for a comprehensive management strategy in such complicated high-risk surgeries. CONCLUSIONS The multidisciplinary collaboration in this case proved effective and yielded significant therapeutic outcomes for a rare case of advanced hepatic, cardiac, and pulmonary AE. The combined approach of ELRA and RA reconstruction under extracorporeal circulation demonstrated distinct advantages of ELRA in treating complex HAE. Meanwhile, assessing diaphragm function during the perioperative period, especially in patients at high risk of developing pulmonary complications and undergoing diaphragmectomy is vital to promote optimal postoperative recovery. For multi-resistant infection, it is imperative to take all possible measures to mitigate the risk of AKI if vancomycin administration is deemed necessary.
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Affiliation(s)
- Rexiati Ruze
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830011, China
| | - Tiemin Jiang
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830011, China
| | - Weimin Zhang
- Department of Cardiac Surgery, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China
| | - Mingming Zhang
- Department of Cardiac Surgery, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China
| | - Ruiqing Zhang
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China
| | - Qiang Guo
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China
| | - Aboduhaiwaier Aboduhelili
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China
| | - Musitapa Zhayier
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China
| | - Ahmad Mahmood
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China
| | - Zhaoxia Yu
- Department of Critical Care Medicine, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China
| | - Jianrong Ye
- Department of Anesthesia, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China
| | - Yingmei Shao
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China.
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830011, China.
| | - Tuerganaili Aji
- Department of Hepatobiliary and Echinococcosis Surgery, Digestive and Vascular Surgery Center, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, 830011, China.
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830011, China.
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Sun T, Yang N, Li L, Zhang X, Liu H, Kusuman N, Chu J, Lü G, Aji T, Bi X, Lin R. sCD155 as a potential marker for diagnosing the vascular invasion in hepatic alveolar echinococcosis. Acta Trop 2024; 255:107203. [PMID: 38604326 DOI: 10.1016/j.actatropica.2024.107203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 03/30/2024] [Accepted: 03/30/2024] [Indexed: 04/13/2024]
Abstract
BACKGROUND Alveolar Echinococcosis (AE) is a malignant zoonotic disease caused by Echinococcus multilocularis infection. Considering whether the lesion is accompanied by vascular invasion (VI) is crucial for treatment strategies. A cost-effective and convenient clinical diagnostic method is urgently needed to supplement current techniques. Consequently, we detected soluble CD155 (sCD155) as a potential biomarker for diagnosing VI in hepatic alveolar echinococcosis (HAE). METHODS Blood samples were from 42 AE patients and 49 healthy controls (HCs). Based on the computed tomography (CT) and contrast-enhanced CT, AE patients were further categorized into HAE with VI (VIAE; 27 cases) and HAE without VI (NVAE; 15 cases). The sCD155 concentration was measured by an enzyme-linked immunosorbent assay (ELISA). Correlations between sCD155 expression levels and clinicopathological features of AE patients were analyzed using SPSS and GraphPad Prism software. RESULTS The sCD155 concentrations in AE patients were significantly higher than in HCs. The serum sCD155 level significantly differed between the VIAE and NVAE groups. The univariate analysis showed that VI of AE was significantly correlated with the sCD155 level when the sCD155 was greater than 11 ng/mL. After adjusting for potential confounding factors, the multivariable analysis showed that sCD155 had an independent effect on VI of HAE. The receiver operating characteristic (ROC) curve showed that sCD155 could differentially diagnose VI of HAE at the cut-off value of 11.08 ng/mL with an area under the curve (AUC) value of 0.75. The sensitivity and specificity were 74.07 % and 66.67 %, respectively; the positive and negative predictive values were 74.07 % and 60.00 %, respectively. CONCLUSION The sCD155 could be a VI biomarker for HAE. Elevated sCD155 levels are indicative of an increased likelihood of concomitant VI in HAE patients, necessitating a thorough evaluation of vascular impairment and the formulation of individualized management strategies.
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Affiliation(s)
- Tao Sun
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, PR China
| | - Ning Yang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, PR China
| | - Liang Li
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, PR China
| | - Xue Zhang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, PR China
| | - Hui Liu
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, PR China
| | - Nuerbaiti Kusuman
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, PR China
| | - Jin Chu
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, PR China
| | - Guodong Lü
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, PR China
| | - Tuerganaili Aji
- Department of Hepatobiliary and Hydatid Diseases, Digestive and Vascular Surgery Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, PR China.
| | - Xiaojuan Bi
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, PR China.
| | - Renyong Lin
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, PR China; Xinjiang Key Laboratory of Echinococcosis, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, PR China.
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Ma W, Ma Z, Shi Y, Pang X, Yimingjiang M, Dang Z, Cui W, Lin R, Zhang W. Comparison of clinicopathological features between cerebral cystic and alveolar echinococcosis: analysis of 27 cerebral echinococcosis cases in Xinjiang, China. Diagn Pathol 2024; 19:90. [PMID: 38956596 PMCID: PMC11218392 DOI: 10.1186/s13000-024-01500-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2024] [Accepted: 05/27/2024] [Indexed: 07/04/2024] Open
Abstract
BACKGROUND Cerebral echinococcosis is relatively rare, and it is important to distinguish cerebral cystic echinococcosis (CCE) from cerebral alveolar echinococcosis (CAE) in terms of pathological diagnosis. We aim to describe the different clinicopathological features among patients with CCE and CAE. METHODS We collected 27 cases of cerebral echinococcosis which were diagnosed in the Department of Pathology of the First Affiliated Hospital of Xinjiang Medical University from January 1, 2012, to June 30, 2023. We compared the patients' clinical characteristics, MRI features, and pathologic manifestations of CCE and CAE. RESULTS Among 27 cases of cerebral echinococcosis, 23 cases were CAE and 4 cases were CCE. The clinical manifestations of both CCE and CAE patients mainly included headache (21 patients, 77.78%), limb movement disorders (6 patients, 22.22%), epileptic seizures (4 patients, 14.81%) and visual disturbances (2 patients, 7.41%). The average onset age of CAE cases was 34.96 ± 11.11 years, which was 9.00 ± 7.26 years in CCE cases. All CAE patients presented with multiple involvements in the brain and extracranial organs while all CCE patients observed a solitary lesion in the brain and 3 CCE cases had no extracranial involvement. Lesions of CCE in MRI showed a single isolated circular, which was well demarcated from the surrounding tissues and with no obvious edema around the lesions, whereas CAE lesions presented as multiple intracranial lesions, with blurred edges and edema around the lesions, and multiple small vesicles could be observed in the lesions. The edge of CAE lesions could be enhanced, while CCE lesions have no obvious enhancement. CCE foci were clear cysts with a wall of about 0.1 cm. Microscopically, the walls of the cysts were characterized by an eosinophilic keratin layer, which was flanked on one side by basophilic germinal lamina cells, which were sometimes visible as protocephalic nodes. While the CAE lesion was a nodular structure with a rough and uneven nodule surface, and the cut section was cystic and solid; microscopically, the CAE lesion had areas of coagulative necrosis, and the proto-cephalic nodes were barely visible. Inflammatory cell areas consisting of macrophages, lymphocytes, epithelioid cells, plasma cells, eosinophils, and fibroblasts can be seen around the lesion. Brain tissues in the vicinity of the inflammatory cell areas may show apoptosis, degeneration, necrosis, and cellular edema, while brain tissues a little farther away from the lesion show a normal morphology. CONCLUSIONS With the low incidence of brain echinococcosis, the diagnosis of echinococcosis and the differential diagnosis of CAE and CCE are challenging for pathologists. Grasping the different clinical pathology characteristics of CAE and CCE is helpful for pathologists to make accurate diagnoses.
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Affiliation(s)
- Wenmei Ma
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, 830054, Xinjiang, China
| | - Zhiping Ma
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Yi Shi
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Xuelian Pang
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Maiweilidan Yimingjiang
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Zhe Dang
- Department of Nuclear Medicine, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Wenli Cui
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
| | - Renyong Lin
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, 830054, Xinjiang, China
| | - Wei Zhang
- Department of Pathology, The First Affiliated Hospital of Xinjiang Medical University, Xinjiang, China.
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Petrone L, Najafi-Fard S, Falasca L, Sbarra S, Teggi A, Nicastri E, Grillo LR, Burocchi M, Ettorre GM, Ludovisi A, Colombo D, Del Nonno F, Goletti D. Evaluation of the Local and Peripheral Immune Responses in Patients with Cystic Echinococcosis. Pathogens 2024; 13:477. [PMID: 38921775 PMCID: PMC11206897 DOI: 10.3390/pathogens13060477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 05/28/2024] [Accepted: 05/30/2024] [Indexed: 06/27/2024] Open
Abstract
BACKGROUND Cystic echinococcosis (CE) cysts may persist for decades because of immune modulation mechanisms. Here, we characterize the cysts and the blood immune responses in patients with CE. METHODS We enrolled 61 patients with CE and 19 control subjects. We received tissue samples from seven patients with CE and a control subject requiring liver cystectomy. The immunohistochemistry evaluation of the immune cell subtypes and cytokines in the pericysts and surrounding liver and the antigen B (AgB)-specific response analysis of whole blood were performed. RESULTS In CE, the pericyst and the surrounding liver parenchyma showed aggregates of CD3+ T lymphocytes, mainly CD4+. B lymphocyte aggregates were present in the liver tissue. Monocytes/granulocytes were rarely observed. Th2 cytokine expression was scarce, whereas IFN-γ expression was present in the CE tissues. The control subject did not show an inflammatory infiltrate. The IL-4-specific response to AgB was increased in the patients with CE compared to the control, and this result was confirmed in a larger cohort (p = 0.003), whereas the IFN-γ-response was similar between the two groups (p = 0.5570). CONCLUSION In patients with CE, CD4+ lymphocytes infiltrate the pericyst and the surrounding liver tissue with a low IL-4/IL-13 expression level and a moderate IFN-γ expression level; moreover, an IL-4 parasite-specific response is detected in the periphery. These results support adventitia involvement in CE immunopathogenesis.
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Affiliation(s)
- Linda Petrone
- Translational Research Unit, National Institute for Infectious Diseases (INMI) “Lazzaro Spallanzani”—IRCCS, 00149 Rome, Italy
| | - Saeid Najafi-Fard
- Translational Research Unit, National Institute for Infectious Diseases (INMI) “Lazzaro Spallanzani”—IRCCS, 00149 Rome, Italy
| | - Laura Falasca
- Laboratory of Electron Microscopy, National Institute for Infectious Diseases “Lazzaro Spallanzani”—IRCCS, 00149 Rome, Italy
| | - Settimia Sbarra
- Translational Research Unit, National Institute for Infectious Diseases (INMI) “Lazzaro Spallanzani”—IRCCS, 00149 Rome, Italy
| | - Antonella Teggi
- Department of Infectious and Tropical Diseases, Sant’Andrea Hospital University of Rome “Sapienza”, 00189 Rome, Italy
| | - Emanuele Nicastri
- Clinical Division of Infectious Diseases, National Institute for Infectious Diseases “Lazzaro Spallanzani”—IRCCS, 00149 Rome, Italy
| | | | - Mirco Burocchi
- Division of General Surgery and Liver Transplantation, San Camillo-Forlanini Hospital, 00152 Rome, Italy
| | - Giuseppe Maria Ettorre
- Division of General Surgery and Liver Transplantation, San Camillo-Forlanini Hospital, 00152 Rome, Italy
| | - Alessandra Ludovisi
- Foodborne and Neglected Parasitoses Unit, Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy
| | - Daniele Colombo
- Pathology Unit, National Institute for Infectious Diseases “Lazzaro Spallanzani”—IRCCS, 00149 Roma, Italy
| | - Franca Del Nonno
- Pathology Unit, National Institute for Infectious Diseases “Lazzaro Spallanzani”—IRCCS, 00149 Roma, Italy
| | - Delia Goletti
- Translational Research Unit, National Institute for Infectious Diseases (INMI) “Lazzaro Spallanzani”—IRCCS, 00149 Rome, Italy
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Erganis S, Sarzhanov F, Al FD, Cağlar K. Comparison of Methods in the Serologic Diagnosis of Cystic Echinococcosis. Acta Parasitol 2024; 69:1122-1131. [PMID: 38551763 PMCID: PMC11182860 DOI: 10.1007/s11686-024-00840-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2023] [Accepted: 03/20/2024] [Indexed: 06/18/2024]
Abstract
PURPOSE Cystic echinococcosis (CE) is caused by the larval form of Echinococcus granulosus. Clinical, radiologic, pathologic, and serologic findings should be evaluated together for the diagnosis of CE. The sensitivity and specificity oalf serologic tests may vary depending on the method used. In this study, we aimed to detect IgG antibodies specific to E. granulosus using indirect hemagglutination assay (IHA), enzyme-linked immunosorbent assay (ELISA), indirect fluorescent antibodies (IFA) and western blot (WB) tests. METHODS In our study, the serum samples of 74 patients sent to our laboratory with suspicion of CE were studied using two different commercial IHA tests, ELISA, IFA and WB test. The test results were evaluated along with radiological findings and histopathological examinations, the latter being the gold standard. RESULTS Of all the patients, 51 (69%) were female and 23 (31%) were male. There was a statistically significant difference between males and females (χ2 = 9.7, p = 0.002). Out of 74 patients, positivity rates for Siemens IHA, Fumouze IHA, ELISA, IFA and WB test were positive as 33 (44.6%), 35 (47.3%), 43 (58.1%), 42 (56.7%) and 38 (51.3%), respectively. The sensitivity and specificity of the tests were as follows: 66.67 and 2.31% for Siemens IHA; 70.83% and 96.15% for Fumouze IHA; 85.42%, and 88.46% for ELISA; 83.33% and 88.46% for IFA; 72.92% and 88.46% for WB test. CONCLUSION There were statistically significant differences in between all five methods (p < 0,001). While the tests with the highest specificity was Fumouze IHA, the test with the highest sensitivity was the ELISA test. It was concluded that IHA and ELISA tests were more practical in practice because of their greater applicability.
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Affiliation(s)
- Sidre Erganis
- Department of Medical Microbiology, School of Medicine, Gazi University, 06490, Ankara, Türkiye.
| | - Fakhriddin Sarzhanov
- Division of Medical Parasitology, Department of Medical Microbiology, School of Medicine, Gazi University, 06490, Ankara, Türkiye
- Faculty of Medicine, Akhmet Yassawi International Kazakh-Turkish University, 161200, Turkestan, Kazakhstan
| | - Funda Doğruman Al
- Division of Medical Parasitology, Department of Medical Microbiology, School of Medicine, Gazi University, 06490, Ankara, Türkiye
| | - Kayhan Cağlar
- Department of Medical Microbiology, School of Medicine, Gazi University, 06490, Ankara, Türkiye
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Lin X, Shao YM, Zhang RQ, Aji T. Applying LASSO logistic regression for the prediction of biliary complications after ex vivo liver resection and autotransplantation in patients with end-stage hepatic alveolar echinococcosis. Eur J Med Res 2024; 29:301. [PMID: 38812045 PMCID: PMC11134669 DOI: 10.1186/s40001-024-01898-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 05/21/2024] [Indexed: 05/31/2024] Open
Abstract
BACKGROUND The purpose of this study was to explore the relevant risk factors associated with biliary complications (BCs) in patients with end-stage hepatic alveolar echinococcosis (HAE) following ex vivo liver resection and autotransplantation (ELRA) and to establish and visualize a nomogram model. METHODS This study retrospectively analysed patients with end-stage HAE who received ELRA treatment at the First Affiliated Hospital of Xinjiang Medical University between August 1, 2010 and May 10, 2023. The least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize the feature variables for predicting the incidence of BCs following ELRA. Multivariate logistic regression analysis was used to develop a prognostic model by incorporating the selected feature variables from the LASSO regression model. The predictive ability, discrimination, consistency with the actual risk, and clinical utility of the candidate prediction model were evaluated using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Internal validation was performed by the bootstrapping method. RESULTS The candidate prediction nomogram included predictors such as age, hepatic bile duct dilation, portal hypertension, and regular resection based on hepatic segments. The model demonstrated good discrimination ability and a satisfactory calibration curve, with an area under the ROC curve (AUC) of 0.818 (95% CI 0.7417-0.8958). According to DCA, this prediction model can predict the risk of BCs occurrence within a probability threshold range of 9% to 85% to achieve clinical net benefit. CONCLUSIONS A prognostic nomogram with good discriminative ability and high accuracy was developed and validated to predict BCs after ELRA in patients with end-stage HAE.
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Affiliation(s)
- Xin Lin
- Centre of Digestive and Vascular Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, Xinjiang, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, 830000, Xinjiang, China
| | - Ying-Mei Shao
- Centre of Digestive and Vascular Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, Xinjiang, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, 830000, Xinjiang, China
| | - Rui-Qing Zhang
- Centre of Digestive and Vascular Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, Xinjiang, China
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, 830000, Xinjiang, China
| | - Tuerganaili Aji
- Centre of Digestive and Vascular Surgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830000, Xinjiang, China.
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Urumqi, 830000, Xinjiang, China.
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Robertson LJ, Woolsey ID, Jiménez-Meléndez A. Current and potential future impacts of food- and water-borne parasites in a changing world: A Norwegian perspective. CURRENT RESEARCH IN PARASITOLOGY & VECTOR-BORNE DISEASES 2024; 5:100181. [PMID: 38883144 PMCID: PMC11178983 DOI: 10.1016/j.crpvbd.2024.100181] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 05/14/2024] [Accepted: 05/21/2024] [Indexed: 06/18/2024]
Abstract
In 2021, the Norwegian Scientific Committee for Food and Environment published a multi-criteria risk ranking of 20 potentially food-borne pathogens in Norway. The pathogens ranked included five parasite taxa (3 species, one genus, one family): Toxoplasma gondii, Echinococcus multilocularis, Giardia duodenalis, Cryptosporidium spp., and Anisakidae. Two of these, T. gondii and E. multilocularis, scored very highly (1st and 3rd place, respectively), Cryptosporidium was about midway (9th place), and G. duodenalis and Anisakidae ranked relatively low (15th and 20th place, respectively). Parasites were found, on average, more likely to present an increasing food-borne disease burden in the future than the other pathogens. Here, we review the current impact of these five potentially food-borne parasites in Norway, and factors of potential importance in increasing their future food-borne disease burden. Climate change may affect the contamination of water and fresh produce with transmission stages of the first four parasites, potentially leading to increased infection risk. Alterations in host distribution (potentially due to climate change, but also other factors) may affect the occurrence and distribution of Toxoplasma, Echinococcus, and Anisakidae, and these, coupled with changes in food consumption patterns, could also affect infection likelihood. Transmission of food-borne pathogens is complex, and the relative importance of different pathogens is affected by many factors and will not remain static. Further investigation in, for example, ten-years' time, could provide a different picture of the relative importance of different pathogens. Nevertheless, there is clearly the potential for parasites to exert a greater risk to public health in Norway than currently occurs.
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Affiliation(s)
- Lucy J Robertson
- Parasitology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), P.O. Box 5003, NO-1432 Ås, Norway
| | - Ian D Woolsey
- Parasitology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), P.O. Box 5003, NO-1432 Ås, Norway
| | - Alejandro Jiménez-Meléndez
- Parasitology, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), P.O. Box 5003, NO-1432 Ås, Norway
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Nassef NE, Shendi SS, Saad AGE, Harba NM, Beshay EVN, Mohamed ASED, Gouda MA. An in vivo appraisal of Punica granatum peel extract's ultrastructural effect on cystic echinococcosis in mice. J Helminthol 2024; 98:e40. [PMID: 38738533 DOI: 10.1017/s0022149x24000300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2024]
Abstract
In the past decade, interest has significantly increased regarding the medicinal and nutritional benefits of pomegranate (Punica granatum) peel. This study examined the effects of using pomegranate peel extract (PGE) alone and in combination with albendazole (ABZ) on ultrastructural and immunological changes in cystic echinococcosis in laboratory-infected mice. Results revealed that the smallest hydatid cyst size and weight (0.48 ± 0.47mm, 0.17 ± 0.18 gm) with the highest drug efficacy (56.2%) was detected in the PGE + ABZ group, which also exhibited marked histopathological improvement. Ultrastructural changes recorded by transmission electron microscopy including fragmentation of the nucleus, glycogen depletion, and multiple lysosomes in vacuolated cytoplasm were more often observed in PGE + ABZ group. IFN-γ levels were significantly increased in the group treated with ABZ, with a notable reduction following PGE treatment, whether administered alone or in combination with ABZ. Thus, PGE enhanced the therapeutic efficiency of ABZ, with improvement in histopathological and ultrastructural changes.
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Affiliation(s)
- Nashaat E Nassef
- Parasitology Department, Faculty of Medicine, Menoufia University, Yassin Abdel Ghaffar St. from Gamal Abdel Nasser St., Shebin El-Kom, Menoufia, Egypt
| | - Sawsan S Shendi
- Department of Clinical and Molecular Parasitology Department, National Liver Institute, Menoufia University, Shebin El-Kom, Menoufia, Egypt
| | - Abdel-Gawad E Saad
- Department of Clinical and Molecular Parasitology Department, National Liver Institute, Menoufia University, Shebin El-Kom, Menoufia, Egypt
| | - Nancy M Harba
- Parasitology Department, Faculty of Medicine, Menoufia University, Yassin Abdel Ghaffar St. from Gamal Abdel Nasser St., Shebin El-Kom, Menoufia, Egypt
| | - Engy V N Beshay
- Parasitology Department, Faculty of Medicine, Menoufia University, Yassin Abdel Ghaffar St. from Gamal Abdel Nasser St., Shebin El-Kom, Menoufia, Egypt
| | | | - Marwa A Gouda
- Department of Clinical and Molecular Parasitology Department, National Liver Institute, Menoufia University, Shebin El-Kom, Menoufia, Egypt
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Bumann S, Kuenzli E, Lissandrin R, Brunetti E, Goblirsch S, Henning L, Tamarozzi F, Neumayr A. Cardiac cystic echinococcosis-A systematic review and analysis of the literature. PLoS Negl Trop Dis 2024; 18:e0012183. [PMID: 38814859 PMCID: PMC11139302 DOI: 10.1371/journal.pntd.0012183] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 04/30/2024] [Indexed: 06/01/2024] Open
Abstract
Human cystic echinococcosis (CE) is a parasitic infection caused by the larval stage of the tapeworm Echinococcus granulosus sensu lato, primarily affecting the liver and lungs. Although the heart is affected in only 0.02-2% of all CE cases, a considerable number of cases have been, and continue to be, published. However, due to the rare occurrence of cardiac CE and the resulting lack of clinical trials, knowledge about various aspects of the disease remains limited. To obtain a clearer picture of anatomical, clinical, diagnostic as well as therapeutic aspects of cardiac CE, we systematically reviewed the literature published between 1965 and 2022. The anatomical pattern of the affected cardiac structures follows the extension of the supplying capillary bed. The majority of patients (82.7%) are symptomatic and present with prolonged non-specific symptoms such as dyspnoea, chest pain and palpitations. Acute complications generally derive from cyst rupture, occur in 18.3% of cases and manifest as embolism, pericardial tamponade, or anaphylactic reaction in 83.2%, 17.8% and 10.9% of these cases, respectively. As for CE cysts localized in other organs, the diagnosis of cardiac CE is made by imaging. Serology plays a minor role due to its limited sensitivity. Unlike abdominal CE cysts, cardiac CE cysts are usually resected independent of their stage (active/inactive), because their presence impairs cardiac performance and carries the risk of long-term sequelae. More than 80% of patients are treated with a single surgical intervention. We found a disease-related case fatality rate of 11.1%. Since local recurrence was reported up to 108 months and secondary CE up to 72 months after surgery, patients should be followed up for a minimum of 10 years.
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Affiliation(s)
- Simone Bumann
- Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Esther Kuenzli
- Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
| | - Raffaella Lissandrin
- Division of Infectious and Tropical Diseases, University of Pavia, IRCCS S. Matteo Hospital Foundation, WHO Collaborating Centre on Clinical Management of Cystic Echinococcosis, Pavia, Italy
| | - Enrico Brunetti
- Division of Infectious and Tropical Diseases, University of Pavia, IRCCS S. Matteo Hospital Foundation, WHO Collaborating Centre on Clinical Management of Cystic Echinococcosis, Pavia, Italy
| | - Sam Goblirsch
- Department of Medicine and Pediatrics, University of Minnesota, Minneapolis, Minnesota, United States of America
| | - Lars Henning
- Department of Public Health and Tropical Medicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Queensland, Australia
| | - Francesca Tamarozzi
- Department of Infectious-Tropical Diseases and Microbiology, WHO Collaborating Centre on Strongyloidiasis and other Neglected Tropical Diseases, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Verona, Italy
| | - Andreas Neumayr
- Swiss Tropical and Public Health Institute, Basel, Switzerland
- University of Basel, Basel, Switzerland
- Department of Public Health and Tropical Medicine, College of Public Health, Medical and Veterinary Sciences, James Cook University, Queensland, Australia
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48
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Zhang C, Li Z, Fu Y, Li T, Hou S, Wang C, Li M, Zhao W. A SIMPLE, QUICK, AND ECONOMICAL METHOD FOR IN VITRO CULTIVATION OF ECHINOCOCCUS MULTILOCULARIS METACESTODE AND GENERATION OF PRIMARY CELLS. J Parasitol 2024; 110:210-217. [PMID: 38811020 DOI: 10.1645/23-100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024] Open
Abstract
Alveolar echinococcosis is considered to be one of the most potentially lethal parasitic zoonotic diseases. However, the molecular mechanisms by which Echinococcus multilocularis interacts with hosts are poorly understood, hindering the prevention and treatment of this disease. Due to the great advantages of cell culture systems for molecular research, numerous attempts have been made to establish primary cell cultures for E. multilocularis. In this study we developed a simple, rapid, and economical method that allows E. multilocularis metacestode tissue blocks to generate daughter vesicles without the continuous presence of host feeder cells in a regular medium. We performed anaerobic, hypoxic (1% O2), normoxic, and semi-anaerobic (in sealed tubes) cultures and found that E. multilocularis metacestode tissues can produce daughter vesicles only in the sealed tubes after 4 wk of incubation. The daughter vesicles cultivated in this system were remarkably enlarged under anaerobic conditions after 8 days of culture, whereas vesicles cultured under hypoxic (1% O2) and normoxic conditions showed only a mild increase in volume. Our in vitro cultivated vesicles showed strong viability and could be used to test antiparasitic drugs, isolate primary cells, and infect animals.
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Affiliation(s)
- Cuiying Zhang
- School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China
- Ningxia Key Laboratory of Prevention and Control of Common Infectious Diseases, Yinchuan, Ningxia 750004, China
| | - Zihua Li
- School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China
| | - Yong Fu
- Qinghai Academy of Animal Sciences and Veterinary Medicine, Qinghai University, Xining, Qinghai 810000, China
| | - Tao Li
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China
| | - Siyu Hou
- School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China
- Ningxia Key Laboratory of Prevention and Control of Common Infectious Diseases, Yinchuan, Ningxia 750004, China
| | - Chan Wang
- School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China
- Ningxia Key Laboratory of Prevention and Control of Common Infectious Diseases, Yinchuan, Ningxia 750004, China
| | - Ming Li
- Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China
| | - Wei Zhao
- School of Basic Medicine, Ningxia Medical University, Yinchuan, Ningxia 750004, China
- Ningxia Key Laboratory of Prevention and Control of Common Infectious Diseases, Yinchuan, Ningxia 750004, China
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49
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Ghanimatdan M, Sadjjadi SM, Mikaeili F, Teimouri A, Jafari SH, Derakhshanfar A, Hashemi-Hafshejani S. Therapeutic effect of curcumin nanoemulsion on cystic echinococcosis in BALB/c mice: a computerized tomography (CT) scan and histopathologic study evaluation. BMC Complement Med Ther 2024; 24:143. [PMID: 38575891 PMCID: PMC10993536 DOI: 10.1186/s12906-024-04451-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2023] [Accepted: 03/21/2024] [Indexed: 04/06/2024] Open
Abstract
BACKGROUND This study aimed to determine the therapeutic efficacy of curcumin nanoemulsion (CUR-NE) in mice infected with Echinococcus granulosus sensu stricto protoscoleces. METHODS Forty-two inbred BALB/c mice were divided into seven groups of six animals each. Six groups were inoculated intra-peritoneally with 1500 viable E. granulosus protoscoleces, followed for six months and used as infected groups. The infected groups were named as: CEI1 to CEI6 accordingly. The 7th group was not inoculated and was named cystic echinococcosis noninfected group (CENI7). CEI1 and CEI2 groups received 40 mg/kg/day and 20 mg/kg/day curcumin nanoemulsion (CUR-NE), respectively. CEI3 received nanoemulsion without curcumin (NE-no CUR), CEI4 received curcumin suspension (CUR-S) 40 mg/kg/day, CEI5 received albendazole 150 mg/kg/day and CEI6 received sterile phosphate-buffered saline (PBS). CENI7 group received CUR-NE 40 mg/kg/day. Drugs administration was started after six months post-inoculations of protoscoleces and continued for 60 days in all groups. The secondary CE cyst area was evaluated by computed tomography (CT) scan for each mouse before treatment and on the days 30 and 60 post-treatment. The CT scan measurement results were compared before and after treatment. After the euthanasia of the mice on the 60th day, the cyst area was also measured after autopsy and, the histopathological changes of the secondary cysts for each group were observed. The therapeutic efficacy of CUR-NE in infected groups was evaluated by two methods: CT scan and autopsied cyst measurements. RESULTS Septal calcification in three groups of infected mice (CEI1, CEI2, and CEI4) was revealed by CT scan. The therapeutic efficacy of CUR-NE 40 mg/kg/day (CEI1 group) was 24.6 ± 26.89% by CT scan measurement and 55.16 ± 32.37% by autopsied cysts measurements. The extensive destructive effects of CUR-NE 40 mg/kg/day (CEI1 group) on the wall layers of secondary CE cysts were confirmed by histopathology. CONCLUSION The current study demonstrated a significant therapeutic effect of CUR-NE (40 mg/kg/day) on secondary CE cysts in BALB/c mice. An apparent septal calcification of several cysts revealed by CT scan and the destructive effect on CE cysts observed in histopathology are two critical key factors that suggest curcumin nanoemulsion could be a potential treatment for cystic echinococcosis.
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Affiliation(s)
- Mohamad Ghanimatdan
- Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Mahmoud Sadjjadi
- Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Fattaneh Mikaeili
- Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Aref Teimouri
- Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Hamed Jafari
- Department of Radiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Amin Derakhshanfar
- Department of Comparative Biomedical Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Saeideh Hashemi-Hafshejani
- Department of Parasitology and Mycology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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50
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Albani CM, Iglesias A, Albanese A, Fuentes G, Orallo D, Maggi M, Elissondo MC. Evaluation of the Protoscolicidal Activity of Humulus lupulus Methanolic Extracts on Echinococcus granulosus Sensu Stricto. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2024; 2024:6251666. [PMID: 38605998 PMCID: PMC11008976 DOI: 10.1155/2024/6251666] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 12/06/2023] [Accepted: 03/23/2024] [Indexed: 04/13/2024]
Abstract
The larval stage of the parasite Echinococcus granulosus sensu lato (s.l) is responsible for cystic echinococcosis (CE), a long-term infection affecting humans and animals worldwide, and constitutes a serious public health concern. If left untreated, CE can cause serious damage to multiple organs, especially the liver and lungs. Regarding the treatment, in the last few years, the use of pharmacological treatment has increased, suggesting that in the future, drug therapy may replace surgery for uncomplicated cysts. However, the only available anthelmintic drug to treat this infection is the albendazole, which has an efficacy that does not exceed 50%. On the basis of the above-mentioned evidence, new and improved alternative treatments are urgently needed. The use of natural products and their active fractions and components holds great promise as a valuable resource for the development of novel and effective therapies. Hop (Humulus lupulus L.) is a bittering agent in the brewing industry for which the sedative, digestive, anti-inflammatory, and antimicrobial effects have been reported. The purpose of this study was to assess the in vitro efficacy of methanolic extracts from the leaves of hop varieties against E. granulosus sensu stricto (s.s) protoscoleces. Varieties Mapuche and Victoria caused a stronger protoscolicidal effect compared to the Bullion, Cascade, and Traful varieties (P < 0.01), coinciding with their highest content of flavonoids, total polyphenols, and saponins. The viability of protoscoleces treated with the varieties Mapuche and Victoria decreased to approximately 50% at days 5 y 8, respectively, showing alterations such as soma contraction and impaired microtriches. After 18 days of treatment with both varieties, protoscoleces were completely altered both structurally and ultrastructurally. In conclusion, the methanolic extracts of the H. lupulus varieties Mapuche and Victoria demonstrated a marked in vitro effect against E. granulosus s.s. protoscoleces. The beer-making industry exclusively uses hop cones, leaving behind large amounts of hop leaves as an agricultural by-product that is not being utilized. On the basis of our study, we propose that hop leaves could also be used as a source of secondary metabolites with anthelmintic activity.
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Affiliation(s)
- Clara María Albani
- Instituto de Investigaciones en Producción Sanidad y Ambiente (IIPROSAM CONICET-UNMdP), Facultad de Ciencias Exactas y Naturales-UNMdP, Centro Científico Tecnológico Mar del Plata-CONICET, Centro de Asociación Simple CIC PBA, Mar del Plata, Argentina
- Laboratorio de Zoonosis Parasitarias, Facultad de Ciencias Exactas y Naturales (FCEyN), Universidad Nacional de Mar del Plata (UNMdP), Mar del Plata, Buenos Aires, Argentina
| | - Azucena Iglesias
- Instituto de Investigaciones en Producción Sanidad y Ambiente (IIPROSAM CONICET-UNMdP), Facultad de Ciencias Exactas y Naturales-UNMdP, Centro Científico Tecnológico Mar del Plata-CONICET, Centro de Asociación Simple CIC PBA, Mar del Plata, Argentina
- Centro de Investigación en Abejas Sociales, FCEyN, UNMdP, Mar del Plata, Buenos Aires, Argentina
| | - Adriana Albanese
- Instituto de Investigaciones en Producción Sanidad y Ambiente (IIPROSAM CONICET-UNMdP), Facultad de Ciencias Exactas y Naturales-UNMdP, Centro Científico Tecnológico Mar del Plata-CONICET, Centro de Asociación Simple CIC PBA, Mar del Plata, Argentina
- Laboratorio de Zoonosis Parasitarias, Facultad de Ciencias Exactas y Naturales (FCEyN), Universidad Nacional de Mar del Plata (UNMdP), Mar del Plata, Buenos Aires, Argentina
| | - Giselle Fuentes
- Instituto de Investigaciones en Producción Sanidad y Ambiente (IIPROSAM CONICET-UNMdP), Facultad de Ciencias Exactas y Naturales-UNMdP, Centro Científico Tecnológico Mar del Plata-CONICET, Centro de Asociación Simple CIC PBA, Mar del Plata, Argentina
- Centro de Investigación en Abejas Sociales, FCEyN, UNMdP, Mar del Plata, Buenos Aires, Argentina
| | - Dalila Orallo
- Departamento de Química y Bioquímica, Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Mar del Plata, Funes 3350, Mar del Plata, Buenos Aires 7600, Argentina
| | - Matías Maggi
- Instituto de Investigaciones en Producción Sanidad y Ambiente (IIPROSAM CONICET-UNMdP), Facultad de Ciencias Exactas y Naturales-UNMdP, Centro Científico Tecnológico Mar del Plata-CONICET, Centro de Asociación Simple CIC PBA, Mar del Plata, Argentina
- Centro de Investigación en Abejas Sociales, FCEyN, UNMdP, Mar del Plata, Buenos Aires, Argentina
| | - María Celina Elissondo
- Instituto de Investigaciones en Producción Sanidad y Ambiente (IIPROSAM CONICET-UNMdP), Facultad de Ciencias Exactas y Naturales-UNMdP, Centro Científico Tecnológico Mar del Plata-CONICET, Centro de Asociación Simple CIC PBA, Mar del Plata, Argentina
- Laboratorio de Zoonosis Parasitarias, Facultad de Ciencias Exactas y Naturales (FCEyN), Universidad Nacional de Mar del Plata (UNMdP), Mar del Plata, Buenos Aires, Argentina
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