Evaluation of a structured treatment discontinuation in patients with inoperable alveolar echinococcosis on long-term benzimidazole therapy: A retrospective cohort study

Abstract

Objectives Alveolar echinococcosis (AE) is an orphan zoonosis of increasing concern in endemic areas, including Europe. It frequently presents in an advanced, inoperable stage, that requires life-long parasitostatic benzimidazole therapy. In some patients, long-term therapy leads to negative anti-Em18 antibody ELISA and PET. It is disputed, whether these patients are truly cured and treatment can be safely discontinued. Our aim was to retrospectively assess long-term outcome of 34 patients with inoperable AE who participated in a previous study to determine feasibility of benzimidazole treatment cessation. Methods Retrospective analysis of medical charts was undertaken in all 34 AE patients who participated in our previous study. Of particular interest were AE recurrence or other reasons for re-treatment in patients who stopped benzimidazole therapy and whether baseline clinical and laboratory parameters help identify of patients that might qualifiy for treatment cessation. Additionally, volumetric measurement of AE lesions on contrast-enhanced cross-sectional imaging was performed at baseline and last follow-up in order to quantify treatment response. Results 12 of 34 patients stopped benzimidazole therapy for a median of 131 months. 11 of these patients showed stable or regressive AE lesions as determined by volumetric measurement. One patient developed progressive lesions with persistently negative anti-Em18 antibody ELISA but slight FDG-uptake in repeated PET imaging. At baseline, patients who met criteria for treatment cessation demonstrated higher lymphocyte count and lower total IgE. Conclusion Treatment cessation is feasible in inoperable AE patients, who demonstrate negative anti-Em18 antibody ELISA and PET on follow-up. Close monitoring including sectional imaging is strongly advised.

Monoclonal antibody-based localization of major diagnostic antigens in metacestode tissue, excretory/secretory products, and extracellular vesicles of Echinococcus species

“…Currently, the Em18 antigen has been mainly used for the follow-up of AE patients under long-term benzimidazole therapy. Negativity of anti-Em18 antibodies for at least two years is one of the parameters used to determine, if benzimidazole therapy in inoperable AE patients can be stopped ( Ammann et al., 2015 ; Deibel et al., 2022 ). Thereby, the Em18 antigen seems to be vital for biological functions and the viability of especially E. multilocularis metacestodes.…”

“…These two antigens are immunologically most likely identical and can be used for a serological parasite-viability assessment after long-term therapy with albendazole in AE patients. A negative II/3-10 or Em18 antibody serology is correlated to a positive treatment outcome and clinical remission in combination with PET-CT ( Ammann et al., 2015 ; Deibel et al., 2022 ; Gottstein et al., 2019 ; Hotz et al., 2022 ). In immunohistochemistry with polyclonal rabbit antibodies directed against the II/3 antigen, the germinal layer and protoscoleces can be visualized.…”

Proteomic profiling of serum extracellular vesicles identifies diagnostic markers for echinococcosis

“…Given the unavailability of serum samples, it is still unclear whether TER ATPase is suitable for early diagnosis of human echinococcosis. The Em18 antigen is known to be a valid marker for follow-up [ 50 ]. Our results showed that, for cured patients, both TPx-1 and TER ATPase had a higher positive rate than the recombinant Em18 protein.…”

Evaluation of Eosinophilic Cationic Protein as a Marker of Alveolar and Cystic Echinococcosis

“…At the time of initial presentation, eosinophilia in the blood is more likely to be seen in CE and is rarely found in AE. All in all, the established markers' total IgE and eosinophil granulocyte counts are limited due to their low sensitivity in CE, but even more limited in AE [10]. The eosinophil cationic protein (ECP) could represent a new promising routine marker measured in serum.…”