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.

Background: Alveolar echinococcosis (AE) is a severe larval tapeworm infection with a variable clinical course of the disease. Reliable imaging techniques and biomarkers are needed to predict the course of the disease. Methods: 179 AE patients that received PET/CT scans between 2008 and 2012 were retrospectively included. From stored blood samples taken on the day of the scan, levels of IgE, parasite-specific serology, amyloid A, C-reactive protein, soluble interleukin 2 receptor, cytokeratin fragments, eosinophilic cell count, and eosinophil cationic protein were measured. Additionally, the current clinical outcome (cured, stable, or progressive disease) after a median duration of 8 years after baseline examination was assessed. Ultimately, an ordinal logistic regression was conducted to evaluate which imaging parameters and biomarkers independently influence the clinical outcome. Results: In general, patients in need of medical treatment or with progressive disease, advanced PNM stages, and positive PET/CT scans exhibited higher levels of the respective biomarkers. However, only the parasite-specific serological markers and total IgE levels differed significantly between clinical groups, WHO PNM stages, and the results of the PET/CT scan. In the multivariate analysis, PET/CT results were a strong predictor of the clinical outcome (OR 8.908, 95%CI 3.019–26.285; p < 0.001), and age at baseline was a moderate predictor (OR 1.031, 95%CI 1.003–1.060; p = 0.029). Conclusions: The PET/CT scan is, preferably in combination with parasite-specific serology and IgE levels, a valuable tool in the clinical management of AE and is able to predict the course of the disease.

Early recognition of sepsis remains difficult in clinical practice because conventional humoral biomarkers such as C-reactive protein, procalcitonin, and interleukin-6 (IL-6) exhibit unfavorable, slow-release kinetics and rise hours after the onset of infection. Flow cytometry enables upstream, cell-based immunomonitoring, but its clinical use is restricted by poor standardization of fluorescence measurements. In this study, the neutrophil cellular response capacity (CRC) was developed and evaluated as a standardized approach for rapid assessment of systemic inflammation in bacteremia and sepsis. The CRC is based on a flow cytometry-based framework that defines a stable maximal stimulation reference point for neutrophil granulocytes. The CRC was evaluated in a human ex vivo whole blood bacteremia model with graded exposure to Escherichia coli and compared with humoral inflammatory markers. Next, the CRC was assessed in a prospective intensive care unit sepsis cohort. Moreover, preliminary validation was performed in an independent sepsis cohort and in patients undergoing cardiac surgery. In the bacteremia model, the CRC of neutrophil markers CD10, CD11b, and CD66b increased in a dose-dependent manner with increasing bacterial burden and detected inflammation at lower pathogen burdens than IL-6 and other humoral mediators, with a superior area under the receiver operating characteristic curve. In clinical sepsis, the CRC discriminated patients from age- and sex-matched healthy volunteers, with the CRC of CD11b showing the highest diagnostic performance. CRC values increased over time in patients with sepsis, consistent with immunological recovery. The maximal stimulation reference point for CD11b remained stable across inflammatory states, cohorts, and instruments. In addition, the CRC more precisely captured the onset and resolution of surgery-induced inflammation than conventional biomarkers. The CRC provides a rapid, standardized, and robust cell-based immunomonitoring tool that outperforms traditional humoral markers in experimental bacteremia and reliably identifies sepsis in clinical cohorts, strongly supporting its use as a novel biomarker for earlier, more precise sepsis diagnosis and monitoring.