Trajectories of cough without a cold in early childhood and associations with atopic diseases.

BACKGROUND: Although children can frequently experience a cough that affects their quality of life, few epidemiological studies have explored cough without a cold during childhood. OBJECTIVES: The objective of the study was to describe the latent class trajectories of cough from one to 10 years old and analyse their association with wheezing, atopy and allergic diseases. METHODS: Questions about cough, wheeze and allergic diseases were asked at 1, 1.5, 2, 3, 4, 5, 6 and 10 years of age in the European prospective cohort of Protection against Allergy: STUdy in Rural Environment (PASTURE). Specific IgE assays were performed at 10 years of age. Questions regarding a cough without a cold were used to build a latent class model of cough over time. RESULTS: Among the 961 children included in the study, apart from the never/infrequent trajectory (59.9%), eight trajectories of cough without a cold were identified: five grouped acute transient classes (24.1%), moderate transient (6.8%), late persistent (4.8%) and early persistent (4.4%). Compared with the never/infrequent trajectory, the other trajectories were significantly associated with wheezing, asthma and allergic rhinitis. For asthma, the strongest association was with the early persistent trajectory (ORa  = 31.00 [14.03-68.51]), which was inversely associated with farm environment (ORa  = 0.39 [0.19-0.77]) and had a high prevalence of cough triggers and unremitting wheeze. Late and early persistent trajectories were also associated with food allergy. Atopic sensitization was only associated with the late persistent trajectory. CONCLUSION: Late and early persistent coughs without a cold are positively associated with atopic respiratory diseases and food allergy. Children having recurrent cough without a cold with night cough and triggers would benefit from an asthma and allergy assessment. Growing up on a farm is associated with reduced early persistent cough.

AE hepatic lesions: correlation between calcifications at CT and FDG-PET/CT metabolic activity.

PURPOSE: To correlate the presence of calcifications in alveolar echinococcosis (AE) hepatic lesions to the metabolic activity in 18 fluorodeoxyglucose positron emission tomography combined with computed tomography (FDG-PET/CT). METHODS: Our institutional review board approved this study. 61 patients (29 women, 32 men, aged from 15 to 86 years) were included in the study. Images of FDG-PET/CT were interpreted by two independent nuclear medicine physicians. AE hepatic lesions were classified as AE lesions with or without hypermetabolic activity. The presence of calcifications was assessed on unenhanced CT scans by two independent radiologists blinded with regard to the metabolic activity of the AE hepatic lesions. Every single calcification the size of which was < 3 mm and non-measurable calcifications which were forming areas with a powdery appearance were considered as microcalcifications. All other types of calcifications were reported as macrocalcifications. Statistical analysis was performed and p value < 0.05 was considered as statistically significant. RESULTS: Microcalcifications and macrocalcifications were present at CT in 95% (58/61) AE hepatic lesions and 43% (26/61) AE hepatic lesions, respectively. Hypermetabolic activity was present at FDG-PET/CT in 93% (57/61) AE hepatic lesions. 98% (56/57) of the AE hepatic lesions presenting with hypermetabolic activity at FDG-PET/CT showed microcalcifications at CT (p = 0.01) when only 40% (23/57) showed macrocalcifications at CT (p = 0.3). 100% (23/23) of the AE hepatic lesions with hypermetabolic activity at FDG-PET/CT and macrocalcifications at CT showed also microcalcifications at CT. CONCLUSIONS: Hypermetabolic activity of AE hepatic lesions at FDG-PET/CT is strongly correlated to the presence of microcalcifications at CT, independently of the presence of macrocalcifications.

Disagreement between Skin Prick Tests and Specific IgE in Early Childhood.

BACKGROUND: Accurate diagnosis of allergic sensitization is essential in clinical practice and allergy research, and the choice of assessment method may have an important impact. The PASTURE study (Protection against Allergy: Study of Rural Environment) examines the influence of exposure to a dairy farm environment on the occurrence of allergy in a cohort of rural European children from birth to 10 years. The aim of our study was to analyze agreement between skin prick tests (SPTs), to aeroallergens and food allergens, and specific IgE and to evaluate the association of SPT with atopic dermatitis in the 204 French children of the PASTURE study. METHODS: SPT, atopic dermatitis assessment, and specific IgE measurements were performed at 1, 4.5, and 6 years. RESULTS: A total of 137 children attended all three visits. The agreement between SPTs and specific IgE was poor except for perennial aeroallergens at 6 years and for an IgE cutoff greater than 0.7 IU/ml (κ = 0.69, 0.5202 - 0.8621). The prevalence of positive SPTs increased with age. Positive SPTs were transient at 1 year, whereas they were persistent between 4.5 and 6 years. Positive SPTs at 1 year were predictive of the occurrence of atopic dermatitis during follow-up. CONCLUSION: SPTs did not have good agreement with serum-specific IgE in early childhood. Both tests (SPT and specific IgE) should be used. Skin allergenic reactivity increased with age and was transient at 1 year but associated with the occurrence of atopic dermatitis.

IL-33 polymorphisms are associated with increased risk of hay fever and reduced regulatory T cells in a birth cohort.

BACKGROUND: IL-33 polymorphisms influence the susceptibility to asthma. IL-33 indirectly induces Th2-immune responses via dendritic cell activation, being important for development of atopic diseases. Furthermore, IL-33 upregulates regulatory T cells (Tregs), which are critical for healthy immune homeostasis. This study investigates associations between IL-33 polymorphisms during the development of childhood atopic diseases and underlying mechanisms including immune regulation of Tregs. METHODS: Genotyping of IL-33-polymorphisms (rs928413, rs1342326) was performed by MALDI-TOF-MS in 880 of 1133 PASTURE/EFRAIM children. In 4.5-year-old German PASTURE/EFRAIM children (n = 99), CD4+ CD25high FOXP3+ Tregs were assessed by flow cytometry following 24-h incubation of PBMCs with PMA/ionomycin, LPS or without stimuli (U). SOCS3, IL1RL1, TLR4 mRNA expression and sST2 protein levels ex vivo were measured in PASTURE/EFRAIM children by real-time PCR or ELISA, respectively. Health outcomes (hay fever, asthma) were assessed by questionnaires at the age of 6 years. RESULTS: rs928413 and rs1342326 were positively associated with hay fever (OR = 1.77, 95%CI = 1.02-3.08; OR = 1.79, 95%CI = 1.04-3.11) and CD4+ CD25high FOXP3+ Tregs (%) decreased in minor allele homozygotes/heterozygotes compared to major allele homozygotes (p(U) = 0.004; p(LPS) = 0.005; p(U) = 0.001; p(LPS) = 0.012). SOCS3 mRNA expression increased in minor allele homozygotes and heterozygotes compared with major allele homozygotes for both IL-33-polymorphisms (p(rs928413) = 0.032, p(rs1342326) = 0.019) and negatively correlated to Tregs. CONCLUSIONS: IL-33-polymorphisms rs928413 and rs1342326 may account for an increased risk of hay fever with the age of 6 years. Lower Tregs and increased SOCS3 in combined heterozygotes and minor allele homozygotes may be relevant for hay fever development, pointing towards dysbalanced immune regulation and insufficient control of allergic inflammation.

Alveolar echinococcosis: correlation between hepatic MRI findings and FDG-PET/CT metabolic activity.

OBJECTIVE: To correlate the appearance of alveolar echinococcosis (AE) hepatic lesions in magnetic resonance imaging (MRI) as defined by Kodama, to the metabolic activity visualized in 18-fluoro-deoxyglucose positron emission tomography combined with computed tomography (PET/CT). MATERIALS AND METHODS: Forty-two patients diagnosed with AE and who underwent both MRI and PET/CT were included. The forty-two hepatic lesions were divided into five types according to Kodama's classification by three independent readers blinded with regard to the PET/CT information. Concerning PET/CT, two independent readers, unaware of the MRI information, considered the results as positive when an increased FDG-uptake was observed at 1 or 3 h after FDG-injection, and as negative when no increased uptake was noted. Inter-observer agreement was assessed by using κ statistics. RESULTS: Forty-two lesions were counted and the mean diameter of overall evaluated lesions was 6.3 cm. One lesion (2.4%) was categorized as type 1, 11 (26.2%) as type 2, 24 (57.1%) as type 3, 3 (7.1%) as type 4, and 3 (7.1%) as type 5. The inter-observer analysis found a κ coefficient of 0.96. All type-1, 90.9% of type-2 and 87.5% of type-3 lesions showed an increased FDG-uptake on PET/CT images. All non-microcystic AE liver lesions (types 4 and 5) showed no abnormal increased FDG-uptake on PET/CT images. The inter-observer analysis at 1 and 3 h found a κ coefficient of 0.95 and 0.92, respectively. CONCLUSIONS: In patients with AE liver lesions, the absence of microcysts on MRI is strongly correlated to a metabolically inactive disease.

Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood.

BACKGROUND: European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. OBJECTIVE: We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. METHODS: From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4(+)CD25(+) forkhead box protein 3 (FOXP3)(+) (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. RESULTS: Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4(+)CD25(+), FOXP3(+) T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. CONCLUSIONS: Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.

Detecting nested clusters of human alveolar echinococcosis.

Recent changes in the epidemiology of alveolar echinococcosis (AE) in Eurasia have led to increasing concerns about the risk of human AE and the need for a thorough evaluation of the epidemiological situation. The aim of this study was to explore the use of a National Register to detect complex distribution patterns on several scales. The data were human AE cases from the FrancEchino register, diagnosed in France from 1982 to 2011. We used the Kulldorff spatial scan analysis to detect non-random locations of cases. We proposed an exploratory method that was based on the successive detection of nested clusters inside each of the statistically significant larger clusters. This method revealed at least 4 levels of disease clusters during the study period. The spatial variations of cluster location over time were also shown. We conclude that National Human AE registers, although not exempted from epidemiological biases, are currently the best way to achieve an accurate representation of human AE distribution on various scales. Finally, we confirm the multi-scale clustered distribution of human AE, and we hypothesize that our study may be a reasonable starting point from which to conduct additional research and explore the processes that underlie such distributions.

Alveolar echinococcosis in solid organ transplant recipients: a case series from two national cohorts.

Alveolar echinococcosis (AE) is a severe parasitic infection caused by the ingestion of Echinococcus multilocularis eggs. While higher incidence and faster evolution have been reported in immunosuppressed patients, no studies have been performed specifically on AE in transplant patients. We searched for all de novo AE cases diagnosed between January 2008 and August 2018 in solid organ transplant (SOT) recipients included in the Swiss Transplant Cohort Study and the FrancEchino Registry. Eight cases were identified (kidney = 5, lung = 2, heart = 1, liver = 0), half of which were asymptomatic at diagnosis. AE diagnosis was difficult due to the low sensitivity (60%) of the standard screening serology (Em2+) and the frequently atypical radiological presentations. Conversely, Echinococcus Western blot retained good diagnostic performances and was positive in all eight cases. Five patients underwent surgery, but complete resection could only be achieved in one case. Moreover, two patients died of peri-operative complications. Albendazole was initiated in seven patients and was well tolerated. Overall, AE regressed in one, stabilized in three, and progressed in one case, and had an overall mortality of 37.5% (3/8 patients). Our data suggest that AE has a higher mortality and a faster clinical course in SOT recipients; they also suggest that the parasitic disease might be due to the reactivation of latent microscopic liver lesions through immune suppression. Western blot serology should be preferred in this population. Finally, surgery should be considered with caution, because of its low success rate and high mortality, and conservative treatment with albendazole is well tolerated.

Title: Échinococcose alvéolaire chez les receveurs d'une greffe d'organe solide : une série de cas de deux cohortes nationales. Abstract: L'échinococcose alvéolaire (EA) est une maladie parasitaire grave causée par l'ingestion d'œufs d'Echinococcus multilocularis. Bien qu'une plus haute incidence et une évolution plus rapide aient été rapportées chez les patients immunodéprimés, aucune étude n'a été conduite spécifiquement sur cette maladie chez les patients transplantés. Nous avons donc listé tous les cas d'échinococcose alvéolaire apparus de novo entre janvier 2008 et août 2018 chez les patients transplantés d'organe solide inclus dans la cohorte Swiss Transplant Cohort Study et le registre FrancEchino. Huit patients ont été identifiés (rein = 5, poumon = 2, cœur = 1, foie = 0), dont la moitié était asymptomatique au moment du diagnostic. Le diagnostic était compliqué par la basse sensibilité (60 %) de la sérologie standard de dépistage (Em2+) et par les présentations radiologiques atypiques des lésions. Les performances diagnostiques du Western Blot n'étaient toutefois pas affectées et ce test était positif chez tous les patients. Sur les cinq patients opérés, une résection complète n'a été possible que dans un cas, tandis que deux patients sont décédés dans les suites de l'opération. L'albendazole a été introduit chez 7 patients et a été bien toléré. Dans l'ensemble, l'EA s'est stabilisée dans 3 cas, a régressé dans un cas et a progressé dans un autre cas, avec une mortalité de 37,5 % (3/8 patients). Nos résultats suggèrent une mortalité plus élevée et une évolution plus rapide de l'EA chez les patients transplantés. Ils suggèrent aussi que la maladie parasitaire pourrait être due à la réactivation de lésions hépatiques microscopiques latentes à la faveur de l'immunosuppression. Le Western Blot devrait être préféré dans cette population. Finalement, la chirurgie devrait être envisagée avec prudence, étant donnés son faible taux de réussite, le nombre élevé de décès peri-opératoires et la bonne tolérance au traitement conservateur par albendazole.

Should possible recurrence of disease contraindicate liver transplantation in patients with end-stage alveolar echinococcosis? A 20-year follow-up study.

Liver transplantation (LT) is currently contraindicated in patients with residual or metastatic alveolar echinococcosis (AE) lesions. We evaluated the long-term course of such patients who underwent LT and were subsequently treated with benzimidazoles. Clinical, imaging, serological, and therapeutic data were collected from 5 patients with residual/recurrent AE lesions who survived for more than 15 years. Since 2004, [(18) F]-2-fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) images were available, and the levels of serum antibodies (Abs) against Echinococcus multilocularis-recombinant antigens were evaluated. Median survival time after LT was 21 years. These patients were from a prospective cohort of 23 patients with AE who underwent LT: 5 of 8 patients with residual/recurrent AE and 4 of 9 patients without residual/recurrent AE were alive in September 2009. High doses of immunosuppressive drugs, the late introduction of therapy with benzimidazoles, its withdrawal due to side effects, and nonadherence to this therapy adversely affected the prognosis. Anti-Em2(plus) and anti-rEm18 Ab levels and standard FDG-PET enabled the efficacy of therapy on the growth of EA lesions to be assessed. However, meaningful variations in Ab levels were observed below diagnostic cutoff values; and in monitoring AE lesions, images of FDG uptake taken 3 hours after its injection were more sensitive than images obtained 1 hour after its injection. In conclusion, benzimidazoles can control residual/recurrent AE lesions after LT. Using anti-rEm18 or anti-Em2(plus) Ab levels and the delayed acquisition of FDG-PET images can improve the functional assessment of disease activity. The potential recurrence of disease, especially in patients with residual or metastatic AE lesions, should not be regarded as a contraindication to LT when AE is considered to be lethal in the short term.

Echinococcus multilocularis and its intermediate host: a model of parasite-host interplay.

Host-parasite interactions in the E. multilocularis-intermediate host model depend on a subtle balance between cellular immunity, which is responsible for host's resistance towards the metacestode, the larval stage of the parasite, and tolerance induction and maintenance. The pathological features of alveolar echinococcosis. the disease caused by E. multilocularis, are related both to parasitic growth and to host's immune response, leading to fibrosis and necrosis, The disease spectrum is clearly dependent on the genetic background of the host as well as on acquired disturbances of Th1-related immunity. The laminated layer of the metacestode, and especially its carbohydrate components, plays a major role in tolerance induction. Th2-type and anti-inflammatory cytokines, IL-10 and TGF-beta, as well as nitric oxide, are involved in the maintenance of tolerance and partial inhibition of cytotoxic mechanisms. Results of studies in the experimental mouse model and in patients suggest that immune modulation with cytokines, such as interferon-alpha, or with specific antigens could be used in the future to treat patients with alveolar echinococcosis and/or to prevent this very severe parasitic disease.

[Échinococcose alvéolaire]. / Alveolar echinococcosis.

Alveolar echinococcosi. Alveolar echinococcosis is a parasitic anthropo-zoonosis which looks like a slow-growing liver cancer. The lesions progressively obstruct hepatic vessels and bile ducts and invade neighboring organs, and it may metastasize to the lung and the brain and possibly all distant organs. Since the 1990s earlier diagnosis by imaging, advances in surgical and less invasive interventions, and prolonged anti-parasitic treatment using albendazole, have totally transformed the prognosis of the disease. However, in Europe, the endemic area has considerably increased, the number of alveolar echinococcosis cases has more than doubled in the previously identified endemic regions, and the disease may now be considered to be an 'opportunistic infection', especially diagnosed in those patients treated with immunosuppressive drugs and biologic agents. Alveolar echinococcosis is currently more and more often diagnosed incidentally, at an early stage of development, and not in the usual 'at risk' regions and populations. This makes differential diagnosis and care management more challenging.

Échinococcose alvéolaire. L'échinococcose alvéolaire est une anthropozoonose parasitaire qui se comporte comme un cancer du foie d'évolution lente. Les lésions envahissent de proche en proche les axes vasculaires et biliaires et les organes de voisinage et sont capables de métastaser, le plus souvent vers le poumon et le cerveau mais potentiellement aussi vers tous les organes. Depuis les années 1990, les progrès en imagerie, l'utilisation judicieuse de la chirurgie et des interventions non chirurgicales et le traitement antiparasitaire par albendazole au long cours ont transformé le pronostic de l'infection. Cependant, en Europe, la zone d'endémie s'est considérablement étendue, le nombre de cas a plus que doublé dans les zones d'endémie « traditionnelles ¼, et la maladie peut maintenant être comptée parmi les infections « opportunistes ¼, touchant tout particulièrement les patients traités par des médicaments ou des agents biologiques immunosuppresseurs. La découverte accidentelle de lésions à la phase précoce d'évolution, et de plus en plus fréquemment hors des zones et des populations habituellement considérées à risque, pose actuellement des problèmes difficiles de diagnostic différentiel et de nouveaux défis pour la prise en charge thérapeutique.

[Parasite-host relationships and treatment]. / Le parasite et ses relations avec ses hôtes.

Alveolar echinococcosis (AE) is a parasitic disease caused by intrahepatic growth of the larval stage of the cestode Echinococcus multilocularis. The main definitive host in Europe is the fox. The adult worms live in the fox intestine and their oncospheres are disseminated by faeces. Wolves, dogs and cats may also serve as definitive hosts. Small rodents--especially voles in Europe and small lagomorphs in Asia--are the natural intermediate hosts. The tumour-like larva is composed of multiple vesicles which produce protoscoleces, the fertile stage of the E. multilocularis metacestode. Carnivores are infected by preying on infected rodents. Like rodents, humans are intermediate hosts and are infected either by eating uncooked vegetables and berries contaminated by faeces of infected carnivores, or by touching such animals. Humans are naturally resistant to metacestode development. Genetic characteristics are involved in susceptibility/resistance to E. multilocularis metacestodes. In humans and other intermediate animal hosts, immune suppression enhances parasite growth, which is normally controlled by cytotoxic mechanisms and delayed-type hypersensitivity. Tolerance of E. multilocularis is due in part to parasite characteristics (especially carbohydrate antigens of the laminated layer) and in part to the "anti-inflammatory/tolerogenic" cytokines IL-10 and TGF-beta. Treatment with interferon-a restores a cytokine balance favorable to the host and might be a new therapeutic option for AE patients. Vaccination is a scientifically sound but economically and politically Utopian means of preventing the disease. Prevention thus relies on simple lifestyle measures: cooking potentially contaminated food, regular treatment of domestic animals with praziquantel, and precautions when touching potentially infected definitive hosts (foxes and dogs).

[Alveolar echinococcosis: how to confirm the diagnosis?]. / Echinococcose alvéolaire: comment affirme-t-on le diagnostic?

Ultrasonography is the first-step exam for the diagnosis of alveolar echinococcosis. Liver involvement commonly appears as an ill-defined infiltration of the liver parenchyma. Lesions are heterogeneous and in most cases hyperechoic, related to fibro-parasitic tissue associated to scattered calcifications. Hypoechoic foci can also be observed, related to necrosis. In 25 % of the cases, ultrasonography discovers atypical aspects that must be known by radiologists working in endemic region for alveolar echinococcosis. Specific serological tests, particularly ELISA and western blot, usually confirm the diagnosis. Therefore, per-cutaneous punction is exceptionally needed to assess the diagnosis. Other imaging techniques are very useful to complete the diagnosis step and to specify vascular and biliary extension, a crucial information for the therapeutic choice. Computed tomography may show small additional parasitic foci, non visualized by ultrasonography. It allows an accurate examination of the lesions particularly in case of very calcified images that could have made ultrasonographic analysis more difficult. Magnetic resonance imaging may be useful for diagnosis showing on T2 weighted images, in cases of fertile lesions, numerous clustered small cysts. Moreover, it is an excellent technique to analyse vascular involvement, particularly for vena cava and hepatic veins, and to diagnose involvement of adjacent organs. Coupled to cholangio-MR, it allows a precise examination of the biliary tree invasion, particularly in the hilum area.

[Alveolar echinococcosis: a disease comparable to a slow growing cancer]. / L'échinococcose alvéolaire: une maladie comparable à un cancer du foie à marche lente.

Alveolar echinococcosis, a parasitic disease due to the larval stage of the cestode Echinococcus multilocularis, is initially located in the liver in 97% of cases. Progression is very slow and the disease remains silent for many years. The developing larva behaves like a slow-growing liver tumor that gradually invades the liver parenchyma, vessels and bile ducts. Marked granulomatosis around the larva, and the subsequent strong reactive fibrosis, contribute to the severity of the disease. Gradual extension to adjacent organs and distant metastases due to haematogenous spread can also occur. Purely extrahepatic alveolar echinococcosis is rare, but physicians in endemic areas should be aware of this possibility. Diagnostic methods have dramatically improved over the past twenty years. The clinical presentation used to be similar to that of liver cancer, with slowly progressivejaundice (due to involvement of the hilum), huge, hard and irregular hepatomegaly, and a chronic Budd-Chiari syndrome due to hepatic vein involvement. Currently, with extensive use of abdominal ultrasonography, alveolar echinococcosis is commonly diagnosed when still asymptomatic. Alveolar echinococcosis may also be revealed by a complication, such as cholangitis due to communication between the parasite mass and the lumen of a bile duct or to pigment stones accumulating above a parasitic biliary stenosis; liver abscess related to centro-parasitic necrosis; or hematemesis due to esophagal varices in case of portal vein involvement. Metastases, especially in the lungs, reveal the disease in 5% of cases.

[Geography of alveolar echinococcosis]. / Où l'échinococcose alvéolaire sévit-elle?

Alveolar echinococcosis is restricted geographically to the colder areas of the northern hemisphere. In France, the highest prevalence is observed in Franche-Comtd. The yearly incidence of AE in endemic areas is generally low (0.02-0.18 per 100,000 inhabitants) but it can exceed 1 per 100,000 locally. E. multilocularis transmission has intensified in traditionally in foxes endemic areas during the last twenty years, and the parasite has extended its range to new areas and countries of Europe. The increasing proximity of fox populations to urban areas may lead to a new epidemiological pattern. Control measures are only applicable at the local scale, and are essentially based on for deworming.

[Treatment of alveolar echinococcosis: a multidisciplinary task]. / Le traitement de l'échinococcose alvéolaire humaine: une approche multidisciplinaire.

Alveolar echinococcosis is characterized by a long asymptomatic period but, without treatment, up to 80% of patients may die within ten years of diagnosis. Owing to a lack of fast-acting and fully effective chemotherapy, partial radical hepatic resection is the only chance of cure. One-third of patients are now treated in this way, and complex vascular and biliary reconstruction procedures are sometimes necessary. Liver transplantation may also be indicated for highly selected patients (about 5%) with life-threatening complications after failure of other treatments. Interventional radiology and endoscopy can be used to drain liver abscesses and/or infected and obstructed bile ducts, either as palliative procedures or as a bridge to radical resection. Parasitostatic benzimidazole therapy, especially based on continuous albendazole administration, is mandatory for at least two years after radical resection, and for life in inoperable patients.

Screening of antigenic vesicular fluid proteins of Echinococcus multilocularis as potential viability biomarkers to monitor drug response in alveolar echinococcosis patients.

PURPOSE: The only drugs available to treat alveolar echinococcosis (AE) are mostly parasitostatic and in many cases prescribed for life. Decision criteria for discontinuation rely on the absence of parasitic viability. The aim of the present study is to search for candidate proteins that may exhibit good potential as biomarkers for viability. EXPERIMENTAL DESIGN: Sixteen serum samples (five healthy controls, 11 patients with AE), are used. AE-patients are classified into three groups "Cured" (n = 2), "ABZ-responders" (n = 4) and "ABZ-nonresponders" (n = 5). Immunoreactive proteins from vesicular fluid (VF) are identified and quantified by LC-MS/MS analysis after immunoprecipitation (IP) using all 16 serum samples. RESULTS: Shotgun analysis of VF lead to the identification of 107 E. multilocularis proteins. Comparative proteomics reveal nine proteins more abundant in IP eluates from ABZ-nonresponder patients (cathepsin b, prosaposin a preprotein, actin modulator protein, fucosidase alpha L1 tissue, gluthatione-S-tranferase, beta galactosidase, elongation factor 2, H17g protein tegumental antigen, and NiemannPick C2 protein). CONCLUSIONS AND CLINICAL RELEVANCE: Detection of antibodies against these proteins by ELISA could be helpful to monitor the course of alveolar echinococcosis under albendazole (ABZ) treatment.

A European survey of perendoscopic treatment of biliary complications in patients with alveolar echinococcosis.

BACKGROUND: Biliary complications represent a turning point in the course of Alveolar Echinococcosis (AE). We conducted a European survey to collect data on the current usage and results of perendoscopic interventions (PEIs) for their treatment. METHODS: Patient's characteristics and follow-up until January 31st, 2015 were recorded using an online questionnaire. RESULTS: From 18 centers 129 PEIs were analyzed in 38 patients; 139 plastic stents were inserted during 85 PEIs; median time between stent placements was significantly longer when 3 stents or more were placed. Initial symptoms disappeared in 95% and long-term bile duct patency was obtained in 73% of cases. Cholangitis was a more frequent complication of the PEIs (10%) than in other indications; intensive lavage of the bile ducts may prevent this complication. CONCLUSION: European centers use perendoscopic biliary drainage as an efficient and safe alternative to surgery to treat AE biliary complications. Insertion of multiple plastic stents delays stent occlusion and leads to effective and prolonged bile duct patency.