[Show abstract][Hide abstract] ABSTRACT: Accreditation of hospitals includes items regarding the existence of Standard Operating Procedures (SOPs); but these documents can be sources of misunderstanding and patient's safety may be jeopardized. We proposed a solution based on the Controlled Language (CL) concept and developed software services to make CL user-friendly to writers. We carried out: 1) deep linguistic analysis of SOP corpora in two medical domains; 2) language modelling to establish two adapted CLs, 3) improvement of home-made CL Authoring Software by developing software modules and a collaborative corpus-based web-accessible platform for the building of terminological and non-terminological resources, 4) evaluation through focus groups and computer-aided CL-writing test sessions. Health professionals and linguists cooperated closely in a field that is quite new to the health domain. The optimized Prolipsia CL Authoring Software appeared to be a good compromise between users’ needs and CL requirements. All actors agreed that benefits would be gained by using the proposed tools, in terms of patient safety and of work organization, institutional cohesion, and decreased liabilities. They also suggested that software solutions able to analyse the quality of existing texts and help correct them would better fit the situation of institutions which have already got a large corpus of (unsatisfactory) texts at their disposal. Such software is currently at an advanced stage of development, with a first version available.
[Show abstract][Hide abstract] ABSTRACT: This review gives a critical update of the situation regarding alveolar echinococcosis (AE) in Europe in humans, based on existing publications and on findings of national and European surveillance systems. All sources point to an increase in human cases of AE in the "historic endemic areas" of Europe, namely Germany, Switzerland, Austria and France and to the emergence of human cases in countries where the disease had never been recognised until the end of the 20th century, especially in central-eastern and Baltic countries. Both increase and emergence could be only due to methodological biases; this point is discussed in the review. One explanation may be given by changes in the animal reservoir of the parasite, Echinococcus multilocularis (increase in the global population of foxes in Europe and its urbanisation, as well as a possible increased involvement of pet animals as definitive infectious hosts). The review also focuses onto 2 more original approaches: (1) how changes in therapeutic attitudes toward malignant and chronic inflammatory diseases may affect the epidemiology of AE in the future in Europe, since a recent survey of such cases in France showed the emergence of AE in patients with immune suppression since the beginning of the 21st century; (2) how setting a network of referral centres in Europe based on common studies on the care management of patients might contribute to a better knowledge of AE epidemiology in the future.
[Show abstract][Hide abstract] ABSTRACT: Human cystic echinococcosis (CE) is known to be endemic in the Tibet Autonomous Region (TAR), China; however, there is relatively little data from hospital records or community prevalence studies, and the situation regarding occurrence of human alveolar echinococcosis (AE) is unclear. Here we review the available reports about human echinococcosis in the seven prefectures of TAR. In addition, two pilot studies by mass screening using ultrasound (with serology) were undertaken (2006/7) in Dangxiong County of Lhasa Prefecture (north central TAR) and Dingqing County of Changdu Prefecture (eastern TAR). In Dangxiong County a prevalence of 9.9% (55/557) for human CE was obtained but no human AE cases were detected. By contrast, in Dingqing County (
= 232 persons screened), 11 CE cases (4.7%) and 12 AE cases (5.2%) (including one mixed CE and AE case) were diagnosed by ultrasound. Hospital records and published reports indicated that CE cases were recorded in all of seven prefectures in Tibet Autonomous Region, and AE cases in four prefectures. Incidence rates of human CE were estimated to range from 1.9 to 155 per 100,000 across the seven prefectures of TAR, with a regional incidence of 45.1 per 100,000. Incidence of AE was estimated to be between 0.6 and 2.8 cases per 100,000. Overall for TAR, human AE prevalence appeared relatively low; however, the pilot mass screening in Dingqing in eastern TAR indicated that human AE disease is a potential public health problem, possibly similar to that already well described in Tibetan communities bordering TAR in north-west Sichuan and south-west Qinghai provinces.
Journal of Helminthology 08/2015; DOI:10.1017/S0022149X15000656 · 1.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The growth potential of the tumor-like Echinococcus multilocularis metacestode (causing alveolar echinococcosis, AE) is directly linked to the nature/function of the periparasitic host immune-mediated processes. We previously showed that Fibrinogen-like-protein 2 (FGL2), a novel CD4+CD25+ Treg effector molecule, was over-expressed in the liver of mice experimentally infected with E. multilocularis. However, little is known about its contribution to the control of this chronic helminth infection.
Key parameters for infection outcome in E. multilocularis-infected fgl2-/- (AE-fgl2-/-) and wild type (AE-WT) mice at 1 and 4 month(s) post-infection were (i) parasite load (i. e. wet weight of parasitic metacestode tissue), and (ii) parasite cell proliferation as assessed by determining E. multilocularis 14-3-3 gene expression levels. Serum FGL2 levels were measured by ELISA. Spleen cells cultured with ConA for 48h or with E. multilocularis Vesicle Fluid (VF) for 96h were analyzed ex-vivo and in-vitro. In addition, spleen cells from non-infected WT mice were cultured with rFGL2/anti-FGL2 or rIL-17A/anti-IL-17A for further functional studies. For Treg-immune-suppression-assays, purified CD4+CD25+ Treg suspensions were incubated with CD4+ effector T cells in the presence of ConA and irradiated spleen cells as APCs. Flow cytometry and qRT-PCR were used to assess Treg, Th17-, Th1-, Th2-type immune responses and maturation of dendritic cells. We showed that AE-fgl2-/- mice exhibited (as compared to AE-WT-animals) (a) a significantly lower parasite load with reduced proliferation activity, (b) an increased T cell proliferative response to ConA, (c) reduced Treg numbers and function, and (d) a persistent capacity of Th1 polarization and DC maturation.
FGL2 appears as one of the key players in immune regulatory processes favoring metacestode survival by promoting Treg cell activity and IL-17A production that contributes to FGL2-regulation. Prospectively, targeting FGL2 could be an option to develop an immunotherapy against AE and other chronic parasitic diseases.
[Show abstract][Hide abstract] ABSTRACT: Any ambiguity in texts used in the communication about vaccines can not only interfere with comprehension, but also generate safety and liability issues. Within a survey on the quality of written protocols for at-risk interventional procedures and sanitary crises, we analyzed documents relating to vaccination, and among them, the "package-leaflet" of an anti-H1N1 influenza vaccine, widely disseminated to the public in 2009-2010. Among the most common mistakes, we observed that 1) language was not always adjusted to the non-specialist's level of knowledge; 2) chronology, logic, consistency, and homogeneity were often missing; 3) crucial pieces of information were disseminated all over the text, 4) use of the passive voice did not distinguish between instructions and information; 5) use of synonyms could be misleading and impair translation. We propose the use of "Controlled language" (CL) to improve the situation. By constraining lexicon, grammar and syntax, CL is a way to write documents that are clear, accurate and devoid of ambiguity. However, the set of rules necessary to write in CL is difficult to memorize. We thus developed authoring software (Redacticiel Prolipsia) to make the creation of a CL by linguists and its use by health professionals easy and adapted to any domain. It may considerably improve the writing of vaccine package inserts/leaflets. It could be used to write information documents about vaccines and their safety, and operating procedures for professionals to prepare, store, and administer vaccines, decide upon proper indication of vaccines, and follow patients after vaccine injection.
Current Drug Safety 04/2015; 10(1-1):41-8. DOI:10.2174/157488631001150407110052
[Show abstract][Hide abstract] ABSTRACT: ‘Echinococcosis’ applies to 2 rather different diseases, due respectively to E. granulosus, ‘cystic echinococcosis’ (CE), and to E. multilocularis, alveolar echinococcosis (AE). Both species differ by their usual animal reservoir, i.e. mostly domestic animals, for E. granulosus, and mostly wild animals, for E. multilocularis. Other species of Echinococcus may also cause disease in humans, E. oligarthrus and E. vogeli have a clinical presentation similar to that of CE and AE, respectively. No specific disease has been attributed until now to the recently identified species, E. shiquicus. Based on their genetic characteristics, E. granulosus has been split into several species: E. granulosus sensu stricto (ex-sheep strain), E. felidis, E. equinus (ex-horse strain, never recognized to infect humans), E. ortleppi (ex-cattle strain), and E. canadensis (ex-camel, pig and cervid strains). The larval stage of Echinococcus spp., also called ‘metacestode’ is characterized by the germinal layer surrounded by the laminated layer. The germinal layer forms ‘buds’, then ‘vesicles’ (cysts), which are filled with a water-like liquid (‘hydatid/cyst/vesicle fluid’). These cysts may be single (typically for CE) or multiple and aggregated (typically for AE). Fertility is characterized by the budding of ‘protoscoleces’ from the germinal layer, and their release into the cyst fluid. The most striking differences between E. granulosus and E. multilocularis lie in the histological aspect of the metacestodes, respectively big cysts with little inflammatory reaction and numerous protoscoleces in CE, and multiple aggregated small cysts with an impressive granulomatous periparasitic infiltration, associated with dense fibrosis, and few or no protoscoleces in AE, hence the different clinical presentations and complications. Pseudo-cysts, due to massive necrosis of the central part of lesion, may occur in advanced AE. CE is usually maintained by the synanthropic domestic cycle (dog/domestic ungulate) and represents a persistent zoonosis in rural livestock-raising areas where humans cohabit with dogs fed on raw livestock offal where the cysts are present. A cycle in wild animals allows E. multilocularis to subsist in nature. It includes voles of a number of different species depending on the area and the lagomorph Ochotona curzionae (on the Tibetan plateau of China), as intermediate hosts, and foxes, wolves and dogs, and less commonly other carnivores as definitive hosts. Larval AE infection with symptoms close to those observed in humans has been recognized in a number of domestic animals and in zoo animals or in exotic pets. Environmental factors play a critical role in E. multilocularis infection in wild animals, resulting in a heterogeneous geographical distribution of the parasite; in many countries, fox urbanization has considerably increased the human population at risk. The burden of both diseases in terms of DALY lost or economic cost has long been underestimated both in humans and animals. Host-parasite interactions in larval echinococcosis depend on a subtle balance between the various immunological mechanisms involved in protection of the host versus tolerance to the parasite. Very rare in AE, IgE-dependent allergic reactions and eosinophilia occur in CE when there are fissures or ruptures in the cyst. AE lesion progression is faster in patients with immune suppression; immunosuppressive treatments in patients with cancer or inflammatory diseases, more frequently administered since the beginning of the XXIst century, have modified the epidemiology and the presentation of AE in Europe during the last 2 decades. XXIst The diagnosis of both diseases in humans relies on imaging. Both CE and AE may remain asymptomatic for a long period of time; and spontaneous death of the metacestode does occur in many infected patients. Ultrasound (US) examination is the basis for diagnosis in patients with liver-related signs and symptoms and for mass screening. Fortuitous diagnosis of CE or AE on abdominal US images taken for another indication is not rare. Complementary imaging exams at diagnosis and for follow-up include CT-scan, Magnetic Resonance Imaging, and for AE only, Positron Emission Tomography 1 and 3 hours after IV injection of 18F-FluoroDesoxyGlucose (FDG-PET). Diagnosis is confirmed by specific serology; however, serological tests are far less sensitive in CE than in AE. The WHO-Informal Working Group on Echinococcosis has proposed a US-based classification of CE cysts (CE-1 to CE-5), and a staging system for AE (PNM classification) which should be used by clinicians to better assess the evolution potential and severity of the disease as well as to facilitate comparison between case series. Until 1980, the treatment of both CE and AE relied only on surgery. Depending on the class, stage, and size of the lesions, a variety of options are now available. For CE it includes short-term (3 months in average) albendazole treatment for small cysts or, at the opposite of the spectrum, long-term albendazole (> 6 months to several years) treatment for disseminated non-operable CE, the PAIR (puncture, aspiration, injection, reaspiration) percutaneous technique for middle-sized liver cysts without daughter vesicles. The current trend for surgery is to remove the whole cyst (‘total cystectomy’) whenever possible to avoid recurrence; ‘partial cystectomy’ with sterilisation of the cyst content by protoscolecide agents is easier to perform in all settings, but more prone to be followed by recurrence and dissemination. In AE, albendazole treatment is the basis for care management: given for a minimum of 2 years after radical surgical resection of the liver lesions, it must be administered for life in all other cases. The current trend for surgery is to avoid palliative surgery and to prefer percutaneous or perendoscopic drainage and stenting of the obstructed bile ducts and/or percutaneous drainage of the central necrotic cavity in advanced cases. In CE as well as in AE, appropriate monitoring of albendazole and of its possible adverse effects is mandatory, and long-term follow-up of each patient is crucial. For both diseases too, however, there is an urgent need to test new chemical or biological compounds for the treatment of patients who cannot be treated by albendazole, and to evaluate therapeutic strategies, including the various types of surgical operations, by prospective studies.
[Show abstract][Hide abstract] ABSTRACT: Human alveolar echinococcosis (AE) is a severe hepatic disease caused by Echinococcus multilocularis. In France, the definitive and intermediate hosts of E. multilocularis (foxes and rodents, respectively) have a broader geographical distribution than that of human AE. In this two-part study, we describe the link between AE incidence in France between 1982 and 2007 and climatic and landscape characteristics. National-level analysis demonstrated a dramatic increase in AE risk in areas with very cold winters and high annual rainfall levels. Notably, 52% (207/401) of cases resided in French communes (smallest French administrative level) with a mountain climate. The mountain climate communes displayed a 133-fold (95% CI: 95-191) increase in AE risk compared with communes in which the majority of the population resides. A case-control study performed in the most affected areas confirmed the link between AE risk and climatic factors. This arm of the study also revealed that populations residing in forest or pasture areas were at high risk of developing AE. We therefore hypothesised that snow-covered ground may facilitate predators to track their prey, thus increasing E. multilocularis biomass in foxes. Such climatic and landscape conditions could lead to an increased risk of developing AE among humans residing in nearby areas.
Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 11/2014; 20(18). DOI:10.2807/1560-7917.ES2015.20.18.21118 · 5.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Positron emission tomography (PET)-computed tomography (CT) using [18F]-fluorodeoxyglucose (FDG) (FDG-PET/CT) is a valuable method for initial staging and follow up of patients with alveolar echinococcosis (AE). However, the cells responsible for FDG uptake have not been clearly identified. The main goal of our study was to evaluate the uptake of PET tracers by the cells involved in the host-parasite reaction around AE lesions as the first step to develop a specific PET tracer that would allow direct assessment of parasite viability in AE. Candidate molecules ([18F]-fluorotyrosine (FET), [18F]-fluorothymidine (FLT), and [18F]-fluorometylcholine (FMC), were compared to FDG by in vitro studies on human leukocytes and parasite vesicles. Our results confirmed that FDG was mainly consumed by immune cells and showed that FLT was the best candidate tracer for parasite metabolism. Indeed, parasite cells exhibited high uptake of FLT. We also performed PET/CT scans in mice infected intraperitoneally with E. multilocularis metacestodes. PET images showed no FDG or FLT uptake in parasitic lesions. This preliminary study assessed the metabolic activity of human leukocytes and AE cells using radiolabeling. Future studies could develop a specific PET tracer for AE lesions to improve lesion detection and echinococcosis treatment in patients. Our results demonstrated that a new animal model is needed for preclinical PET imaging to better mimic human hepatic and/or periparasitic metabolism.
[Show abstract][Hide abstract] ABSTRACT: Smad family proteins are essential cellular mediators of the transforming growth factor-β superfamily. In the present study, we identified two members of the Smad proteins, Smad8 and Smad4 homologues (termed as EgSmadE and EgSmadD, respectively), from Echinococcus granulosus, the causative agent of cystic echinococcosis (CE). Phylogenetic analysis placed EgSmadE in the Smad1, 5, and 8 subgroup of the R-Smad sub-family and EgSmadD in the Co-Smad family. Furthermore, EgSmadE and EgSmadD attained a high homology to EmSmadE and EmSmadD of E. multilocularis, respectively. Both EgSmadE and EgSmadD were co-expressed in the larval stages and exhibited the highest transcript levels in activated protoscoleces, and their encoded proteins were co-localized in the sub-tegumental and tegumental layer of the parasite. As shown by yeast two-hybrid and pull-down analysis, EgSmadE displayed a positive binding interaction with EgSmadD. In addition, EgSmadE localized in the nuclei of Mv1Lu cells (mink lung epithelial cells) upon treatment with human TGF-β1 or human BMP2, indicating that EgSmadE is capable of being translocated into nucleus, in vitro. Our study suggests that EgSmadE and EgSmadD may take part in critical biological processes, including echinococcal growth, development, and parasite-host interaction.
Parasitology Research 07/2014; 113(10). DOI:10.1007/s00436-014-4040-4 · 2.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
An increased incidence of alveolar echinococcosis (AE) in patients with immunosuppression (IS) has been observed; our aim was to study this association and its characteristics.
Fifty AE cases with IS-associated conditions (ISCs) before or at AE diagnosis were collected from the French AE registry (1982-2012, 509 cases). There were 30 cancers, 9 malignant hematological disorders, 14 chronic inflammatory diseases, 5 transplants, and 1 case of AIDS; 9 patients had ≥2 ISCs. Characteristics of the 42 IS/AE cases and the 187 non-IS/AE cases diagnosed during the period 2002-2012 were statistically compared.
There was a significant increase in IS/AE cases over time. Risk factors did not differ between IS/AE and non-IS/AE patients. However, AE was more frequently an incidental finding (78% vs 42%) and was diagnosed at earlier stages (41% vs 23%) in IS/AE than in non-IS/AE patients. Serology was more often negative (14% vs 1%) and treatment efficacy was better (51% regression after 1-year treatment vs 27%) in IS/AE patients. All IS/AE patients but 7 took IS drugs; 7 received biotherapeutic agents. When not concomitant, AE occurred in IS patients within a 48-month median time period. Atypical presentation and abscess-, hemangioma-, and metastasis-like images delayed AE diagnosis in 50% of IS/AE patients, resulting in inappropriate treatment. Liver images obtained for 15 patients 1-5 years before diagnosis showed no AE lesions. Albendazole efficacy was good, but 19 of 48 treated patients experienced side effects.
Patients with immunosuppression are at increased risk for occurrence, delayed diagnosis, and progression of AE.
[Show abstract][Hide abstract] ABSTRACT: The risks and benefits of traditional cheeses, mainly raw milk cheeses, are rarely set out objectively, whence the recurrent confused debate over their pros and cons. This review starts by emphasizing the particularities of the microbiota in traditional cheeses. It then describes the sensory, hygiene, and possible health benefits associated with traditional cheeses. The microbial diversity underlying the benefits of raw milk cheese depends on both the milk microbiota and on traditional practices, including inoculation practices. Traditional know-how from farming to cheese processing helps to maintain both the richness of the microbiota in individual cheeses and the diversity between cheeses throughout processing. All in all more than 400 species of lactic acid bacteria, Gram and catalase-positive bacteria, Gram-negative bacteria, yeasts and moulds have been detected in raw milk. This biodiversity decreases in cheese cores, where a small number of lactic acid bacteria species are numerically dominant, but persists on the cheese surfaces, which harbour numerous species of bacteria, yeasts and moulds. Diversity between cheeses is due particularly to wide variations in the dynamics of the same species in different cheeses. Flavour is more intense and rich in raw milk cheeses than in processed ones. This is mainly because an abundant native microbiota can express in raw milk cheeses, which is not the case in cheeses made from pasteurized or microfiltered milk. Compared to commercial strains, indigenous lactic acid bacteria isolated from milk/cheese, and surface bacteria and yeasts isolated from traditional brines, were associated with more complex volatile profiles and higher scores for some sensorial attributes. The ability of traditional cheeses to combat pathogens is related more to native antipathogenic strains or microbial consortia than to natural non-microbial inhibitor(s) from milk. Quite different native microbiota can protect against Listeria monocytogenes in cheeses (in both core and surface) and on the wooden surfaces of traditional equipment. The inhibition seems to be associated with their qualitative and quantitative composition rather than with their degree of diversity. The inhibitory mechanisms are not well elucidated. Both cross-sectional and cohort studies have evidenced a strong association of raw-milk consumption with protection against allergic/atopic diseases; further studies are needed to determine whether such association extends to traditional raw-milk cheese consumption. In the future, the use of meta-omics methods should help to decipher how traditional cheese ecosystems form and function, opening the way to new methods of risk–benefit management from farm to ripened cheese.
International journal of food microbiology 05/2014; 177(54):136–154. DOI:10.1016/j.ijfoodmicro.2014.02.019 · 3.08 Impact Factor