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.

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.

[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.

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.

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.

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.

Innovation in hepatic alveolar echinococcosis imaging: best use of old tools, and necessary evaluation of new ones.

Hepatic Alveolar Echinococcosis (HAE), caused by larvae of Echinococcus multilocularis, is a rare but potentially lethal parasitic disease. The first diagnostic suspicion is usually based on hepatic ultrasound exam performed because of abdominal symptoms or in the context of a general checkup; HAE diagnosis may thus also be an incidental finding on imaging. The next step should be Computed Tomography (CT) or Magnetic Resonance Imaging (MRI). They play an important role in the initial assessment of the disease; with chest and brain imaging, they are necessary to assess the PNM stage (parasite lesion, neighboring organ invasion, metastases) of a patient with AE. Performed at least yearly, they also represent key exams for long-term follow-up after therapeutic interventions. Familiarity of radiologists with HAE imaging findings, especially in the endemic regions, will enable earlier diagnosis and more effective treatment. Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) is currently considered to be the only noninvasive, albeit indirect, tool for the detection of metabolic activity in AE. Delayed acquisition of images (3 hrs after FDG injection) enhances its sensitivity for the assessment of lesion metabolism and its reliability for the continuation/withdrawal of anti-parasite treatment. However, sophisticated equipment and high cost widely limit PET/CT use for routine evaluation. Preliminary studies show that new techniques, such as contrast-enhanced ultrasound (US), Dual Energy CT or Spectral CT, and Diffusion-Weighted MRI, might also be useful in detecting the blood supply and metabolism of lesions. However, they cannot be recommended before further evaluation of their reliability in a larger number of patients with a variety of locations and stages of AE lesions.

Non-surgical and non-chemical attempts to treat echinococcosis: do they work?

Cystic echinococcosis (CE) and alveolar echinococcosis (AE) are chronic, complex and neglected diseases. Their treatment depends on a number of factors related to the lesion, setting and patient. We performed a literature review of curative or palliative non-surgical, non-chemical interventions in CE and AE. In CE, some of these techniques, like radiofrequency thermal ablation (RFA), were shelved after initial attempts, while others, such as High-Intensity Focused Ultrasound, appear promising but are still in a pre-clinical phase. In AE, RFA has never been tested, however, radiotherapy or heavy-ion therapies have been attempted in experimental models. Still, application to humans is questionable. In CE, although prospective clinical studies are still lacking, therapeutic, non-surgical drainage techniques, such as PAIR (puncture, aspiration, injection, re-aspiration) and its derivatives, are now considered a useful option in selected cases. Finally, palliative, non-surgical drainage techniques such as US- or CT-guided percutaneous biliary drainage, centro-parasitic abscesses drainage, or vascular stenting were performed successfully. Recently, endoscopic retrograde cholangiopancreatography (ERCP)-associated techniques have become increasingly used to manage biliary fistulas in CE and biliary obstructions in AE. Development of pre-clinical animal models would allow testing for AE techniques developed for other indications, e.g. cancer. Prospective trials are required to determine the best use of PAIR, and associated procedures, and the indications and techniques of palliative drainage.

A new data management system for the French National Registry of human alveolar echinococcosis cases.

Alveolar echinococcosis (AE) is an endemic zoonosis in France due to the cestode Echinococcus multilocularis. The French National Reference Centre for Alveolar Echinococcosis (CNR-EA), connected to the FrancEchino network, is responsible for recording all AE cases diagnosed in France. Administrative, epidemiological and medical information on the French AE cases may currently be considered exhaustive only on the diagnosis time. To constitute a reference data set, an information system (IS) was developed thanks to a relational database management system (MySQL language). The current data set will evolve towards a dynamic surveillance system, including follow-up data (e.g. imaging, serology) and will be connected to environmental and parasitological data relative to E. multilocularis to better understand the pathogen transmission pathway. A particularly important goal is the possible interoperability of the IS with similar European and other databases abroad; this new IS could play a supporting role in the creation of new AE registries.

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.

A historical view of alveolar echinococcosis, 160 years after the discovery of the first case in humans: part 1. What have we learnt on the distribution of the disease and on its parasitic agent?

Since the first 2 cases observed in southern Germany and the correct identification of a parasite at the origin of the disease by the famous scientist Rudolf Virchow in 1855, the borders of the endemic area of alveolar echinococcosis (AE) have never stopped to expand. The parasite was successively recognized in Switzerland, then in Russia, Austria and France which were long considered as the only endemic areas for the disease. Cases were disclosed in Turkey in 1939; then much attention was paid to Alaska and to Hokkaido, in Japan. The situation totally changed in 1991 after the recognition of the Chinese endemic areas by the international community of scientists. The world map was completed in the beginning of the 21st century by the identification of AE in most of the countries of central/eastern Europe and Baltic States, and by the recognition of cases in central Asia. Up to now, the disease has however never been reported in the South hemisphere and in the United Kingdom. In the mid-1950s, demonstration by Rausch and Schiller in Alaska, and by Vogel in Germany, of the distinction between 2 parasite species responsible respectively for cystic echinococcosis ("hydatid disease") and AE put an end to the long-lasting debate between the "dualists", who believed in that theory which eventually proved to be true, and the "unicists", who believed in a single species responsible for both diseases. At the end of the 20th century, molecular biology fully confirmed the "dualist" theory while adding several new species to the initially described E. granulosus; within the past decade, it also confirmed that little variation existed within Echinococcus (E.) multilocularis species, and that AE-looking infection in some intermediate animal hosts on the Tibetan plateau was indeed due to a new species, distinct from E. multilocularis, named E. shiquicus. Since the 1970s, the unique ecological interactions between the landscape, the hosts, and E. multilocularis have progressively been delineated. The important role of the rodent/lagomorph reservoir size for the maintenance of the parasite cycle has been recognized within the last 2 decades of the 20th century. And the discovery of a close relationship between high densities of small mammals and particularities in land use by agriculture/forestry has stressed the responsibility of political/economic decisions on the contamination pressure. Urbanization of foxes in Europe and Japan and the major role of dogs in China represent the new deals at the beginning of the 21st century regarding definitive hosts and prevention measures.

Northwestern China: a place to learn more on oesophageal cancer. Part two: gene alterations and polymorphisms.

In the first part of this review, some behavioural and environmental risk factors playing important roles in the development of Kazakh's oesophageal squamous cell carcinoma (OSCC) were presented. Although all individuals have been exposed to the same environment and share the same behaviour, some of them will not develop OSCC. Thus, gene susceptibility and/or gene polymorphism are unavoidably involved. The molecular events underlying the initiation and progression of OSCC remain, however, poorly understood. In the second part of our review of OSCC in northwestern China, especially in the high-risk Kazakh population, some recent progress in the study of the molecular biology underlying oesophageal carcinogenesis, including chromosome deletions and loss of heterozygocity, polymorphisms of genes involved in xenobiotic metabolizing and DNA repair, and genetic alterations of transcriptional factors and apoptosis genes are presented. Results obtained in this high-risk population are compared with those obtained in other areas that are also known to be at high risk for OSCC, and whenever possible, with those studies performed in European, American or Australian low-risk areas. Recent advances in the investigation of the proteomics and microRNA biomarkers potentially useful for an earlier diagnosis and/or prognosis of OSCC are also discussed.

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.

Northwestern China: a place to learn more on oesophageal cancer. Part one: behavioural and environmental risk factors.

Oesophageal squamous cell carcinoma (OSCC) remains a public health problem in many countries, especially in emerging and developing countries. Epidemiology of OSCC is characterized by marked differences in prevalence between countries/regions/ethnical groups. The highest incidence in the world is reached by populations living in specific areas of northwestern Xinjiang, China where age-adjusted mortality may reach 150 of 100 000. In fact, there are also marked differences among the various geographical areas and the various ethnic groups within the region, which suggests specific risk factors. Behavioural factors include those factors which are common to all 'high-risk populations', such as tobacco smoking and alcohol drinking. However, the very unusual sex ratio (1.2 : 1.0) and young age range of OSCC occurrence suggests the involvement of additional early risk factors shared by males and females, and which are different from those studied in other 'high-risk' areas of the world, including China, such as LinXian area. These include drinking very hot and salted tea, boiled with milk; a diet rich in meat, especially salted, dry and/or smoked meat, and dairy products; and a diet poor in fresh fruit and vegetables. The combination of hot drinks (such as milk, tea and soups) and high-degree spirit drinks, and hard food (bread, meat and cheese), together with poor oral hygiene and tooth loss, is likely to add mechanical injury of the oesophagus to other factors linked to climate characteristics of the area (drought) and dietary habits, which promote a sodium and nitrosamine-rich diet. Association of early and severe hypertension in the same populations at high risk of OSCC might likely raise more attention. Human papilloma virus (HPV) infection, and especially HPV 16/18 E6/E7, with gene mutations and association with p53 overexpression, may contribute to the extremely high incidence of OSCC observed in Xinjiang, and could be accessible to prevention. Infection may especially be a crucial additional factor in the Uygur population in which not only HPV infection but also infection with other oncogenic viruses, such as HHV8, are highly prevalent. Genetic polymorphism might interact with viruses and/or viral products to promote carcinogenesis. These observations in northwestern China suggest that usually neglected factors, such as sodium excess and viral infection, could be taken into more account when studying OSCC risk factors in other parts of the world, especially Europe.