Abstract
Epidemiological studies have demonstrated that most humans infected with Echinococcus spp. exhibit resistance to disease. When infection leads to disease, the parasite is partially controlled by host immunity: in case of immunocompetence, the normal alveolar echinococcosis (AE) or cystic echinococcosis (CE) situation, the metacestode grows slowly, and first clinical signs appear years after infection; in case of impaired immunity (AIDS; other immunodeficiencies), uncontrolled proliferation of the metacestode leads to rapidly progressing disease. Assessing Echinococcus multilocularis viability in vivo following therapeutic interventions in AE patients may be of tremendous benefit when compared with the invasive procedures used to perform biopsies. Current options are F18-fluorodeoxyglucose-positron emission tomography (FDG-PET), which visualizes periparasitic inflammation due to the metabolic activity of the metacestode, and measurement of antibodies against recEm18, a viability-associated protein, that rapidly regresses upon metacestode inactivation. For Echinococcus granulosus, similar prognosis-associated follow-up parameters are still lacking but a few candidates may be listed. Other possible markers include functional and diffusion-weighted Magnetic Resonance Imaging (MRI), and measurement of products from the parasite (circulating antigens or DNA), and from the host (inflammation markers, cytokines, or chemokines). Even though some of them have been promising in pilot studies, none has been properly validated in an appropriate number of patients until now to be recommended for further use in clinical settings. There is therefore still a need to develop reliable tools for improved viability assessment to provide the sufficient information needed to reliably withdraw anti-parasite benzimidazole chemotherapy, and a basis for the development of new alternative therapeutic tools.
Highlights
The genus Echinococcus includes more than seven different species plus multiple genotypes [38]
The correlation we found between images of microvesicles on Magnetic Resonance Imaging (MRI) and positive fluorodeoxyglucose-positron emission tomography (FDG-Positron Emission Tomography (PET)) is likely explained by more numerous and metabolically active immune cells in those areas of the lesions where active vesicles with clearly differentiated solid and liquid components are present [2]
The regulatory T-cell effector Fibrinogen-Like Protein 2 (FGL2) is a recent additional candidate to discriminate between patients with active and inactive lesions: its role as an important mediator of the tolerance status in E. multilocularis infection has received experimental confirmation [64]; preliminary results have shown that its soluble form is significantly increased in the serum of patients with alveolar echinococcosis (AE) compared to healthy subjects; its association with disease course and prognosis is still under investigation (Junhua Wang, personal communication)
Summary
The genus Echinococcus includes more than seven different species plus multiple genotypes [38]. Echinococcus granulosus sensu lato (the small dog tapeworm) represents the most common species and occurs in both hemispheres; predominantly affected regions include the Mediterranean area, Eastern Europe, parts of South America, parts of Africa, and Central Asia/Western China Both parasites cause life-threatening diseases of serious public health and economic concern worldwide [58]. Periparasitic cells of the immune response exhibit a ‘‘granulomatous’’ arrangement and are directly in contact with the organ parenchyma on the one hand, and with the laminated layer of the budding daughter vesicles on the other This process is often referred to as ‘‘progressive tumor-like growth’’, and leads to the formation of a large and heterogeneous parasitic mass consisting of mostly peripheral, actively proliferating, sites, and in many cases, centrally located necrotic tissue. Non-invasive methods would be preferred by the majority of clinicians who express remarkably strong demand for improved tools to assess in vivo the viability or non-viability status of treated hepatic and extra-hepatic echinococcosis lesions
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