Diagnostic and follow-up performance of serological tests for different forms/courses of alveolar echinococcosis

Bruno Gottstein; Anja Lachenmayer; Guido Beldi; Junhua Wang; Bernadette Merkle; Xuan Lan Vu; Ursula Kurath; Norbert Müller

doi:10.1016/j.fawpar.2019.e00055

Diagnostic and follow-up performance of serological tests for different forms/courses of alveolar echinococcosis

Food Waterborne Parasitol. 2019 May 8:16:e00055. doi: 10.1016/j.fawpar.2019.e00055. eCollection 2019 Sep.

Authors

Bruno Gottstein^{1

2}, Anja Lachenmayer³, Guido Beldi³, Junhua Wang¹, Bernadette Merkle¹, Xuan Lan Vu¹, Ursula Kurath¹, Norbert Müller¹

Affiliations

¹ Institute of Parasitology, Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
² Institute for Infectious Diseases, Medical Faculty, University of Bern, Bern, Switzerland.
³ Department of Visceral Surgery and Medicine, Visceral Surgery, Inselspital University Hospital Bern and University Bern, Bern, Switzerland.

Abstract

Diagnosis of alveolar echinococcosis (AE) is predominantly based on imaging procedures combined with immunodiagnostic testing. In the present study, we retrospectively analyzed the performance of four serological tests (EgHF-ELISA, Em2-ELISA, recEm18-ELISA and Em-Immunoblotting) for initial diagnosis and subsequent monitoring of AE patients. Overall, 101 AE patients were included, grouped according to treatment options and immune status as follows: (A) curative surgical treatment (n = 45 patients), (B) non-radical or palliative surgical treatment (n = 11), (C) benzimidazoles only (n = 20), (D) immunocompromised with radical surgical treatment (n = 11), (E) immunocompromised with benzimidazoles only (n = 4), and finally a group of 10 AE patients (F) that were considered to present so-called "abortive" lesions. Initial (i.e. pretreatment) ELISA-based diagnosis for patients in groups A to E revealed overall diagnostic sensitivities of 95% for EgHF, 86% for Em2, and 80% for recEm18, respectively. Comparatively, the diagnostic sensitivity of Em-Immunoblotting was higher with an overall value of 98%. In group F, only Em-Immunoblotting had an excellent diagnostic sensitivity (100%), whereas the ELISAs had poor sensitivities of 30% (EgHF- and Em2-ELISA) or even 0% (recEm18-ELISA). Serological monitoring of AE patients showed a clear association between a curative development of disease (induced either by surgery or benzimidazole medication) and a negativization in the ELISAs. This effect was most pronounced for the recEm18-ELISA, where 56% negativized following diagnosis/treatment, as compared to 36% for the EgHF-ELISA, and 37% for the Em2-ELISA, respectively. After radical surgery, the mean time until negativization in the recEm18-ELISA was 2.4 years (SD 1.6). This was significantly shorter than the mean 3.9 years (SD 2.5) in those AE patients with non-radical, palliative surgery or ABZ treatment who were able to negativize during the study period (p = 0.048). Conclusively, Em-Immunoblotting appears as the most sensitive test to diagnose active as well as inactive ("abortive") AE-cases. The inclusion of the ELISAs completes the initial diagnostic picture and offers valuable additional information. Conversely, recEm18-ELISA appears as the currently best serological tool to monitor a regressive and putatively curative course of AE in treated patients.

Keywords: ABZ, Albendazole; AE, Alveolar echinococcosis; CE, Cystic echinococcosis; Diagnosis; ELISA; ELISA, Enzyme-linked immunosorbent assay; Echinococcus multilocularis; EgHF, Echinococcus granulosus hydatid fluid; Em, Echinococcus multilocularis; EmVF, Echinococcus multilocularis vesicular fluid; FDG-PET/CT, fluorodeoxyglucose Positron Emission Tomography/Computed Tomography; Follow-up serology; Immunoblotting; MRI, Magnetic Resonance Imaging; US, Ultrasonography.