{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:58:54Z","timestamp":1790506734824,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,2,12]],"date-time":"2022-02-12T00:00:00Z","timestamp":1644624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Human alveolar echinococcosis (AE), which is caused by the cestode Echinococcus (E.) multilocularis, is an epidemiologically relevant issue in modern medicine and still poses a diagnostic and therapeutic challenge. Since diagnosis mainly relies on imaging procedures and serological testing, we retrospectively and comparatively analyzed the performance of an Echinococcus IgG screening ELISA, whole serum IgE, and two specific confirmatory ELISA platforms using the defined E. multilocularis antigens Em2-Em18 (Em2+) and recombinant Em18 (recEm18). With special emphasis on the clinical usefulness of recEm18, we correlated the laboratory results with clinical characteristics and imaging findings in a large and well-characterized cohort of N = 124 AE patients, who were followed over several years after either surgical plus subsequent pharmacological treatment or pharmacotherapy alone. All patients had routinely received PET-CTI every two years. Our data reveal strong correlations for both Echinococcus IgG and recEm18 with tracer uptake in PET-CTI and parasitic lesion size and number, suggesting additional clinical usefulness of recEm18 for certain constellations only, while IgG and Em2+ still appear reasonable and sensitive screening methods for initial diagnosis of AE. With this study, we aim to contribute to further optimizing medical care of AE patients. For instance, it might be reasonable to consider the replacement of some PET-CTI follow-ups by imaging procedures with less radiation exposure or serological means alone. Further studies that clarify the correlation of serological markers with ultrasound criteria might be particularly useful, and further retrospective as well as prospective investigations are justified in this context.<\/jats:p>","DOI":"10.3390\/pathogens11020239","type":"journal-article","created":{"date-parts":[[2022,2,13]],"date-time":"2022-02-13T20:34:45Z","timestamp":1644784485000},"page":"239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Evaluation of Serological Markers in Alveolar Echinococcosis Emphasizing the Correlation of PET-CTI Tracer Uptake with RecEm18 and Echinococcus-Specific IgG"],"prefix":"10.3390","volume":"11","author":[{"given":"Julian Frederic","family":"Hotz","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, A-1090 Vienna, Austria"},{"name":"Division of Infectious Diseases, Department of Internal Medicine III, Ulm University Hospital, D-89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4882-6816","authenticated-orcid":false,"given":"Lynn","family":"Peters","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine III, Ulm University Hospital, D-89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Kapp-Schw\u00f6rer","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine III, Ulm University Hospital, D-89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Theis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine III, Ulm University Hospital, D-89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Eberhardt","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Ulm University Hospital, D-89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Essig","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene, Ulm University Hospital, D-89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6669-3741","authenticated-orcid":false,"given":"Beate","family":"Gr\u00fcner","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Internal Medicine III, Ulm University Hospital, D-89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen Benjamin","family":"Hagemann","sequence":"additional","affiliation":[{"name":"Institute of Medical Microbiology and Hygiene, Ulm University Hospital, D-89081 Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/j.rvsc.2020.11.010","article-title":"Echinococcus granulosus sensu lato and Echinococcus multilocularis: A review","volume":"135","author":"Woolsey","year":"2021","journal-title":"Res. Vet. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/S0140-6736(03)14573-4","article-title":"Echinococcosis","volume":"362","author":"McManus","year":"2003","journal-title":"Lancet"},{"key":"ref_3","first-page":"Doc01","article-title":"Comprehensive diagnosis and treatment of alveolar echinococcosis: A single-center, long-term observational study of 312 patients in Germany","volume":"5","author":"Gruener","year":"2017","journal-title":"GMS Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"S283","DOI":"10.1016\/j.parint.2005.11.041","article-title":"WHO classification of alveolar echinococcosis: Principles and application","volume":"55","author":"Kern","year":"2006","journal-title":"Parasitol. Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/PAS.0000000000001374","article-title":"Pathology of echinococcosis: A morphologic and immunohistochemical study on 138 specimens with focus on the differential diagnosis between cystic and alveolar Echinococcosis","volume":"44","author":"Reinehr","year":"2020","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/j.ijpara.2021.10.003","article-title":"Advances in the treatment, diagnosis, control and scientific understanding of taeniid cestode parasite infections over the past 50 years","volume":"51","author":"Lightowlers","year":"2021","journal-title":"Int. J. Parasitol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3077","DOI":"10.1007\/s00436-021-07262-0","article-title":"Recent advances in ultrasound in the diagnosis and evaluation of the activity of hepatic alveolar echinococcosis","volume":"120","author":"Yangdan","year":"2021","journal-title":"Parasitol. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.actatropica.2009.11.001","article-title":"Expert consensus for the diagnosis and treatment of cystic and alveolar echinococcosis in humans","volume":"114","author":"Brunetti","year":"2010","journal-title":"Acta Trop."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Tamarozzi, F., Silva, R., Fittipaldo, V.A., Buonfrate, D., Gottstein, B., and Siles-Lucas, M. (2021). Serology for the diagnosis of human hepatic cystic echinococcosis and its relation with cyst staging: A systematic review of the literature with meta-analysis. PLoS Negl. Trop. Dis., 15.","DOI":"10.1371\/journal.pntd.0009370"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e00050","DOI":"10.1016\/j.fawpar.2019.e00050","article-title":"Surgical treatment strategies for hepatic alveolar echinococcosis","volume":"15","author":"Salm","year":"2019","journal-title":"Food Waterborne Parasitol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1097\/QCO.0000000000000093","article-title":"Acceptance of standardized ultrasound classification, use of albendazole, and long-term follow-up in clinical management of cystic echinococcosis: A systematic review","volume":"27","author":"Tamarozzi","year":"2014","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1055\/s-0041-1730925","article-title":"Hepatic alveolar echinococcosis","volume":"41","author":"Spahr","year":"2021","journal-title":"Semin. Liver Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12392","DOI":"10.3748\/wjg.v21.i43.12392","article-title":"Proposal of an ultrasonographic classification for hepatic alveolar echinococcosis: Echinococcosis multilocularis Ulm classification-ultrasound","volume":"21","author":"Kratzer","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_14","first-page":"3155","article-title":"Evaluation of the diagnostic value of the immunoblotting and ELISA tests using recombinant Em18 antigen in human alveolar echinococcosis from Xingjiang China","volume":"16","author":"Bi","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e00055","DOI":"10.1016\/j.fawpar.2019.e00055","article-title":"Diagnostic and follow-up performance of serological tests for different forms\/courses of alveolar echinococcosis","volume":"16","author":"Gottstein","year":"2019","journal-title":"Food Waterborne Parasitol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1128\/JCM.01111-09","article-title":"Serological monitoring of progression of alveolar echinococcosis with multiorgan involvement by use of recombinant Em18","volume":"47","author":"Ishikawa","year":"2009","journal-title":"J. Clin. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"792","DOI":"10.4269\/ajtmh.2009.80.792","article-title":"Close relationship between clinical regression and specific serology in the follow-up of patients with alveolar echinococcosis in different clinical stages","volume":"80","author":"Tappe","year":"2009","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1128\/CVI.00026-10","article-title":"Immunoglobulin G subclass responses to recombinant Em18 in the follow-up of patients with alveolar echinococcosis in different clinical stages","volume":"17","author":"Tappe","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.5114\/ceh.2019.89480","article-title":"The usefulness of commercially available serological tests in the diagnosis and monitoring of treatment in patients with alveolar echinococcosis","volume":"5","author":"Sulima","year":"2019","journal-title":"Clin. Exp. Hepatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"S267","DOI":"10.1016\/j.parint.2005.11.053","article-title":"Imaging aspects and non-surgical interventional treatment in human alveolar echinococcosis","volume":"55","author":"Delabrousse","year":"2006","journal-title":"Parasitol. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"102356","DOI":"10.1016\/j.parint.2021.102356","article-title":"PET\/CT helps to determine treatment duration in patients with resected as well as inoperable alveolar echinococcosis","volume":"83","author":"Husmann","year":"2021","journal-title":"Parasitol. Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1051\/parasite\/2014072","article-title":"Innovation in hepatic alveolar echinococcosis imaging: Best use of old tools, and necessary evaluation of new ones","volume":"21","author":"Liu","year":"2014","journal-title":"Parasite"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ammann, R.W., Stumpe, K.D., Grimm, F., Deplazes, P., Huber, S., Bertogg, K., Fischer, D.R., and Muellhaupt, B. (2015). Outcome after discontinuing long-term benzimidazole treatment in 11 patients with non-resectable alveolar echinococcosis with negative FDG-PET\/CT and anti-EmII\/3-10 serology. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003964"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4753","DOI":"10.4049\/jimmunol.1501365","article-title":"Cellular dynamics of memory B cell populations: IgM+ and IgG+ memory B cells persist indefinitely as quiescent cells","volume":"195","author":"Jones","year":"2015","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/0035-9203(89)90512-9","article-title":"Em2-ELISA for the follow-up of alveolar echinococcosis after complete surgical resection of liver lesions","volume":"83","author":"Gottstein","year":"1989","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.jhep.2004.06.015","article-title":"Immunosurveillance of alveolar echinococcosis by specific humoral and cellular immune tests: Long-term analysis of the Swiss chemotherapy trial (1976\u20132001)","volume":"41","author":"Ammann","year":"2004","journal-title":"J. Hepatol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/2\/239\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:18:08Z","timestamp":1760134688000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/11\/2\/239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,12]]},"references-count":26,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2]]}},"alternative-id":["pathogens11020239"],"URL":"https:\/\/doi.org\/10.3390\/pathogens11020239","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,12]]}}}