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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.

Since intracellular survival of all chlamydiae depends on the manipulation of the host cell through type III secreted effector proteins, their characterization is crucial for the understanding of chlamydial pathogenesis. We functionally characterized the putative type III secreted Chlamydia abortus protein CAB063, describe its intracellular localization and identified pro-and eukaryotic binding partners. Based on an experimental infection model and plasmid transfections, we investigated the subcellular localization of CAB063 by immunofluorescence microscopy, immunoelectron microscopy, and Western blot analysis. Pro-and eukaryotic targets were identified by co-immunofluorescence, coimmunoprecipitation, and mass spectrometry. Transmission electron microscopy and flow cytometry were used for morphological and functional investigations on host cell apoptosis. CAB063 localized in the nuclear membrane of the host cell nucleus and we identified the chaperone HSP70 and lamin A/C as pro-and eukaryotic targets, respectively. CAB063-dependent morphological alterations of the host cell nucleus correlated with increased apoptosis rates of infected and CAB063-transfected cells. We provide evidence that CAB063 is a chaperone-folded type III secreted C. abortus virulence factor that targets lamin thereby altering the host cell nuclear membrane structure. This process may be responsible for an increased apoptosis rate at the end of the chlamydial developmental cycle, at which CAB063 is physiologically expressed.