[Angele experiment: innovative care paths for allergy sufferers]. / Expérimentation Angele : des parcours de soins innovants pour les patients allergiques.

The Angele project (for Allergies complexes: prise en charge globale, diététique et environnementale) is an article 51 experiment in shared care pathways in allergology. These care paths, dedicated to patients with allergies to house dust mites and/or food, involve collaboration between doctors and paramedics. The aim of this initiative is to optimize patient care by structuring their care pathways. This article presents these pathways and the preliminary results of the experiment.

A comprehensive meta-analysis of Brucella infections in aquatic mammals.

The presence of Brucella infections was documented in a large number of aquatic mammals, affecting wild animals living in oceans, seas, lakes and rivers within both northern and southern hemispheres. Through meta­regression analysis, this study provides acom prehensive view of the prevalence of Brucella spp. in aquatic mammals, identifying risksu bgroups as well as most common sampling and testing methods. Brucella ceti and Brucella pinnipedialis represent the main marine Brucella spp., with documented enzootic potential, for which information on standardized diagnostic methods for the implementation of efficient screening and monitoring programs is needed. A total of 71 articles investigating the occurrence of brucellosis in aquatic mammals have been reported since 1987. The prevalence of brucellosis in males (30.42%) was significantly higher than females (18.59%). The family of Delphinidae was the most studied among aquatic mammals with a total prevalence of 39.66%. Our meta­regression analysis showed a strong and significant association between the prevalence of Brucella spp. in mammals and water temperature (C = 0.02, p value = 0.003), while no significant correlation was found with water salinity (C = ­ 0.09; p value = 0.10). At least 130 species of aquatic mammals have been identified as potential hosts for Brucella spp. There is no systematic veterinary inspection and global or local requirements for the monitoring of brucellosis in aquatic mammals. The association of brucellosis prevalence and water temperature warrants further studies to assess the potential direct and indirect impacts of climate change on brucellosis in aquatic mammals. This study would help to determine the basis of adaptive management strategies in order to control enzootic brucellosis in wild aquatic mammals.

Isolation of Brucella melitensis biovar 1 from human milk confirms breastfeeding as a possible route for infant infection.

Brucellosis during pregnancy is associated with major concerns for mothers but, it is still not clear whether the infection could be transmitted through breastfeeding to newborns. This study aimed at evaluating the shedding of Brucella melitensis through human milk. We describe phenotypic and genotypic characterization of Brucella isolate from human milk. The characterized isolate by Bruce-ladder PCR, AMOS PCR and biotyping confirmed the presence of Brucella melitensis biovar 1 from human milk. However, the breastfeeding of newborn baby induced no serious abnormality, although occasional weakness, loss of appetite and vomiting were reported by the parents. All Brucella serological tests including RBT, SAT and 2 ME test were also positive for the baby and her mother, although the blood culture was negative for the baby. Evaluation of the blood DNA from mother and her baby also confirm the presence of Brucella melitensis in the blood samples. Therefore, the isolation of B. melitensis biovar 1 from human milk as well as presence of Brucella melitensis in the blood samples confirms breastfeeding as a possible route for infant infection.

Brucellosis in Iranian livestock: A meta-epidemiological study.

Brucellosis is a widespread zoonotic disease affecting human and livestock health. This meta-epidemiological study is aiming to draw a comprehensive picture of the Brucella prevalence in Iranian livestock, trying to estimate most affected subgroups as well as the most appropriate methods and sampling conditions for brucellosis screening programs. A literature search was performed among data published between 1 January 1970 and July 2020. Different subgroups were compared according to animal species, gender, age, sampling season, sampling locations as well as the diagnostic method used for brucellosis screening. To determine heterogeneity of studies, Chi-squared test was used and a random effect model (REM) estimated the pooled prevalence among subgroups. A total of 45 publications, comprising 240 studies/data-reports, were evaluated. A significant increase in the number of studies was found over time (Coefficient = 0.151, p value < 0.001). The most studied species in Iran was cow (n = 75), followed by sheep (n = 63), goat (n = 45), camel (n = 40) and Buffalo (n = 16). The most identified Brucella species in livestock were Brucella melitensis (n = 50), Brucella abortus (n = 39), mix infection of B. melitensis and B. abortus (n = 11) and vaccine strain of B. melitensis Rev1 (n = 4). PCR-based tests were the most common applied diagnostic method (n = 140), while the highest prevalence rate of positive samples was obtained by indirect ELISA (69%). The prevalence of brucellosis was significantly higher in females (10.91%) compared to males (8.23%). The meta-epidemiological study of brucellosis in Iranian livestock would help to strengthen surveillance, control and prevention approaches to counter the spread of this zoonotic disease.

The global epidemiology of Brucella infections in terrestrial wildlife: A meta-analysis.

Brucellosis is a widespread zoonotic disease with serious consequences on human and animal health. Brucella infections were reported in many terrestrial wild animals, from subtropical and temperate regions to arctic regions. In many areas, the epidemiology of brucellosis in wildlife is closely associated with the occurrence of the disease in livestock. Some wild species may contribute to the re-introduction of Brucella infections in livestock (spillback), even in officially brucellosis-free (OBF) regions. Through meta-regression analysis, this study draws a global picture of the prevalence of Brucella spp. in terrestrial wild animals, trying to determine most affected subgroups as well as preferential sampling and screening methods. For this purpose, a literature search was carried out among publications published from 1983 to 2019. Different subgroups were compared according to animal species, feeding, gender, age as well as the method used for sampling and for brucellosis diagnostic. To determine heterogeneity of studies, chi-squared test was used and a random-effects model (REM) estimated the pooled prevalence among subgroups. A total of 68 publications, comprising 229 data reports/studies, were selected. The most-reported Brucella species in wildlife was Brucella abortus, and the highest prevalence rate was found in American bison, Bison bison (39.9%) followed by Alpine ibex, Capra ibex (33%). Serology was the most widely applied diagnostic approach (66%), while PCR appeared to be highly sensitive (36.62% of positive results). The gender of animals showed no significant association with the prevalence of brucellosis (p > .05). Blood samples and visceral organs constituted the great majority of specimen used for the detection of Brucella spp., while lymph nodes showed a high prevalence of positive samples (94.6%). The present study provides insight into the global epidemiology and enzootic potential of brucellosis in wild terrestrial animals worldwide, aiming at helping the appropriate authorities to strengthen prevention, surveillance and control strategies.

The association between the incidence of COVID-19 and the distance from the virus epicenter in Iran.

Since the first official report of the spread of SARS-CoV-2 infections in the city of Qom in mid-February, Iran has become the country most affected by the COVID-19 epidemic in the Middle East. All Iranian provinces are now affected, although to a different extent. The aim of the present study was to evaluate whether the distance from the epicenter of the infection (Qom) or demographic factors such as population density and the ratio of the elderly population are associated with the incidence of COVID-19 in different Iranian provinces. For the purpose of determining whether the distance from the virus epicenter could be associated with the spread of infection, linear regression analysis was performed using STATA 12.0 software. The association of the incidence of COVID-19 with the population density and the ratio of the population over 65 years old in 31 Iranian provinces was also evaluated. According to our results, a strong association was found between the incidence of COVID-19 in Iranian provinces and their respective distance from Qom (p < 0.001; C = -0.68). The incidence of COVID-19 in Iranian provinces was also positively associated with the ratio of the population over 65 years old (p = 0.002; C = 0.53), while no significant association with population density was found (p = 0.39; C = 0.16). These results suggest that the implementation of travel restrictions from highly affected areas to other provinces could considerably reduce the rate of transmission of the disease throughout the country. Also, provinces with a higher proportion of elderly people (over 65) were identified as particularly at risk for the spread of SARS-CoV-2 infections. These results will contribute to better management of the COVID-19 outbreak in Iran, taking into account demographic and geographic characteristics of different provinces.

Contamination of milk and dairy products by Brucella species: A global systematic review and meta-analysis.

Brucellosis is known as an influential zoonosis in different regions worldwide, with significant effects on the reproductive performance of livestock. Considering the high incidence of brucellosis in dairy products and further negative impacts on food safety, the present study was aimed to systematically investigate prevalence worldwide among published data regarding the identification of Brucella spp. in dairy products. In this regard, some databases, i.e., Scopus, PubMed, Embase, and Web of Science have been searched to retrieve all related articles regarding the incidence of Brucella contaminations in dairy products from 1 January 1983 to 1 April 2019. The prevalence of Brucella spp. in unpasteurized dairy products based on countries, WHO regions, and dairy product subgroups were evaluated and statistically compared. Based on the findings, the prevalence of Brucella spp. in dairy products increased while the GDP (C = 0.17, P-value < 0.001) and HDI (C = 0.19, P-value < 0.001) ranking decreased. Also, the highest prevalence of Brucella contamination in dairy products was noted in buffalo (25.91%) and goat (17.90%), respectively. The lowest and highest prevalence of Brucella spp. were observed in the Western Pacific (15.32%) and the Southeast Asia region (25.55%), respectively. Also, the rank order of WHO regions based on odds ratio (OR) was Southeast Asia region (2.84) > Eastern Mediterranean (2.41) > Region of America (1.65) > European Region (1.54) > Africa region (1.46) > Western Pacific (reference). The results of this study showed that decreasing poverty and an increase in the level of education in societies could reduce the prevalence of Brucella spp. in dairy products. The outcome of the current investigation can be used for the implementation of sustainable intervention and prevention strategies in affected regions.

A primary investigation of the relation between the incidence of brucellosis and climatic factors in Iran.

Brucella spp. are Gram-negative coccobacilli that may grow in different media and environmental conditions for extended periods of time. The survivals of these bacteria in the environment have an important impact on the epidemiology of brucellosis worldwide. The effect of climate on the incidence of certain zoonotic infectious diseases, (recently referred to as climate-sensitive zoonosis) is now well established. The aim of this study was to evaluate the relation between the incidence of brucellosis and climatic parameters in Iran, an important endemic region for brucellosis with diverse climate. The information on the incidence of human brucellosis in different Iranian provinces for 2016 has been provided by the Ministry of Health and Medical Education, Iran. Annual meteorological data collected between 2015 and 2016 were obtained from the Iranian Meteorological organization (IMO). A regression analysis of the incidence of brucellosis was performed via STATA 14.0 and the heterogeneity among observations was determined via Cochrane's Q-test and I2 statistic. If I2 index was higher than 50%, heterogeneity was considered as considerable. The results of regression analyses revealed a negative significant association between mean ambient air temperature and brucellosis incidence (C = - 0.022, P value = 0.004). Likewise, a positive significant association was found between number of frosty days and brucellosis incidence (C = 0.002, p value = 0.003). Other metrological parameters showed no significant effect on the human brucellosis incidence. Although our results suggest a high degree of temperature sensitivity in regards to the brucellosis incidence in Iran, this study opens up prospects for further investigations regarding environmental conditions and climatic changes influencing the spatial distributions and seasonal/annual cycle of this zoonotic pathogen worldwide.

Year-to-year variation of the elemental and allergenic contents of Ailanthus altissima pollen grains: an allergomic study.

The Ailanthus altissima pollen (AAP) has been reported as an emerging aeroallergen worldwide. This paper aims at examining the allergen pattern and the elemental composition of A. altissima pollen collected during two consecutive seasons (2014 and 2015). A gel-based allergomic study and SEM coupled to energy-dispersive X-ray (EDX) analysis have been carried out in order to evaluate the allergenic and elemental composition of AAP in two consecutive years. The IgE reactive patterns of 2014 and 2015 AAP PBS extracts were compared using the serum of a 31-year-old woman suffering from severe pollinosis symptoms to AAP. The EDX analysis revealed an important year-to-year variation in the ratios of some polluting elements such as nickel, sulfur, aluminum, lead, and copper. Gel alignments and comparative immunoproteomic analyses showed differential protein expression and IgE reactive patterns between AAPs collected in 2014 and 2015 pollinating seasons. From 20 distinct IgE-reactive spots detected in AAP extracts, 13 proteins showed higher expression in 2014 sample, while 7 allergen candidates exhibited an increased expression in AAP collected in 2015. Matrix-assisted laser desorption ionization-MS/MS analyses led to the identification of 13 IgE-binding proteins with confidence, all belonging to well-known allergenic protein families, i.e., enolase, calreticulin, and pectate lyase. Overall, the 2014 AAP showed higher concentrations of urban polluting elements as well as an increased expression of allergenic pectate lyase isoforms of about 52 kDa. This study demonstrates that the implementation of allergomic tools for the safety assessment of newly introduced and invasive plant species would help to the comprehensive monitoring of proteomic and transcriptomic alterations involving environmental allergens.

Cypress Pollinosis: from Tree to Clinic.

Cypress (Cupressus sp.pl) is a genus within the Cupressaceae family. This family covers all of the Earth's continents except for Antarctica, and it includes about 160 species. The most important taxa for allergic diseases belong to five different genera: Cupressus, Hesperocyparis, Juniperus, Cryptomeria, and Chamaecyparis. Cupressaceae species share a common pollen type that can even include the genus Taxus (Taxaceae) when this plant is also present. As Juniperus oxycedrus pollinates in October, Cupressus sempervirens in January and February, Hesperocyparis arizonica (prev. Cupressus arizonica) in February and March, and Juniperus communis in April, the symptomatic period is long-lasting. Due to global warming, the pollination period tends to last longer, and there is a trend for Cupressaceae bioclimate niches to migrate north. In Mediterranean areas, C. sempervirens (Italian cypress or Mediterranean cypress) is by far the most common pollinating species. It accounts for half of the total pollination level. The group 1 major allergens belong to the pectate-lyase family, and members share 70 to 97% sequence homology within the different Cupressaceae. Group 2 allergens correspond to the polygalacturonase protein family, while group 3, a minor allergen, belongs to the family of "thaumatin-like proteins," a pathogenesis-related protein 5. Group 4 allergens are Ca++-binding protein (4 EF-hands). Aside from these four groups, about 15 other allergens have been reported. Prominent among these is a basic low-molecular mass cross-reactive allergen that was identified recently, and which is suspected to be involved in pollen food syndromes which are common with peach and citrus. The prevalence of cypress allergy in the general population ranges from 0.6 to 3%, depending on the degree of exposure to the pollen. Depending on the geographic area and the studied population, 9 to 65% of outpatients consulting an allergist may have sensitization to cypress pollen. Repeated cross-sectional studies performed at different time intervals have demonstrated a threefold increase in the percentage of cypress allergy around the Mediterranean area. Risk factors include a genetic predisposition and/or a strong exposure to pollen, and the natural history of cypress allergy allows identification of a subgroup of patients as allergic rather than atopic. Concerning the clinical expression, rhinitis is the most prevalent symptom, while conjunctivitis is the most disabling. Pharmacological treatment of cypress allergies is not different from that of other seasonal allergies. Immunotherapy has been used, initially by subcutaneous injections, but currently mostly through the sublingual route. Although clinical trials have included only a limited number of patients, it has proven effective and safe. Avoidance can be implemented at the individual level, as well as at the community level, through the use of alternative plants, low-pollinating cypresses, or by trimming hedges before pollination.

Double One-Dimensional Electrophoresis (D1-DE) Adapted for Immunoproteomics.

The classical proteomics approach for the identification of allergen candidates consists on the separation of proteins by high-resolution two-dimensional electrophoresis (2-DE) with subsequent IgE immunoblotting and further analysis of IgE-reactive protein spots with mass spectrometry. In this approach at least two gels most be run. One gel is used for staining and the other is for immunoblotting by antibodies labeled with specific immunostains. Additional functional characterizations require either protein purification or 2-DE replicates and appear to be time- and reagent-consuming. Here we described a modified double one-dimensional electrophoresis (D1-DE) allowing the conversion of a protein spot previously visualized by 2-DE into an extended protein band. In D1-DE, the purity of the protein of interest is similar to 2-DE spots, but its abundance is many times higher than what can be found in a 2-DE single spot allowing many other functional analyses from a single D1-DE separation.

The Use of Combinatorial Hexapeptide Ligand Library (CPLL) in Allergomics.

The recent progress of proteomic protocols led to more efficient protein extraction and concentration procedures to remove nonprotein interfering compounds present in the starting material and to increase the concentration of underrepresented proteins. Combinatorial hexapeptide ligand libraries (CPLL) were recently applied to both plant- and animal-derived tissues for capturing the low- and very low-abundance allergens. Several IgE-binding proteins which were previously absent or poorly represented by using conventional proteomics tools have been detected and characterized through a CPLL-based approach. In the present chapter, a protocol based on improved protein extraction and enrichment by CPLL, allowing the immunochemical characterization of several "hidden allergens" in cypress pollen, is described in detail.

Pollen/Fruit Syndrome: Clinical Relevance of the Cypress Pollen Allergenic Gibberellin-Regulated Protein.

A pollen/food-associated syndrome (PFAS) has been described between peach and cypress pollen. Cross-reactive allergens were characterized which belong to the Gibberellin-regulated protein (GRP) family, BP14 in cypress pollen and Pru p 7 in peach. GRP are small cationic protein with anti-microbial properties. A patient suffering from a peach/cypress syndrome was explored clinically and biologically using 2 types of immunoglobulin E (IgE) multiarray microchip, immunoblots and a basophil activation test to assess the clinical relevance of various extracts and purified allergens from fruits or cypress pollen. In addition to PR10 sensitization, the patient showed specific IgE to Pru p 7, BP14 and allergen from pomegranate. These last 3 allergens and allergenic sources are able to induce ex vivo basophil activation characterized by the monitoring of the expression of CD63 and CD203c, both cell surface markers correlated with a basophil mediator release. Up to 100% of cells expressed CD203c at 50 ng/mL of BP14 protein. In contrast, snakin-1, a GRP from potato sharing 82% sequence identity with Pru p 7 did not activate patient's basophils. These results strongly suggest that, like Pru p 7, BP14 is a clinically relevant allergenic GRP from pollen. Allergen members of this newly described protein family are good candidates for PFAS where no cross-reactive allergens have been characterized.

Human brucellosis caused by raw dairy products: A review on the occurrence, major risk factors and prevention.

Despite considerable efforts made to address the issue of brucellosis worldwide, its prevalence in dairy products remains difficult to estimate and represents an important public health issue in many areas of the globe today. This is partly explained by the increasing tendency for consumption of raw dairy products, making the prevention and control of this zoonosis even more critical. This review summarizes reports published since the early 2000s on human brucellosis caused by contaminated dairy products and the systems of evaluation and assessment which are used to improve the diagnosis, surveillance, control and prevention of the disease. For this purpose, five comprehensive electronic databases were investigated and relevant studies were identified for systematic review. The design and quality of the studies revealed notable variation, especially in the methods used for the detection and characterization of Brucella spp. This report provides helpful information about the health risk associated with the consumption of raw milk and relevant preventive strategies.

Antiinflammatory peptides: current knowledge and promising prospects.

BACKGROUND: Inflammation is part of the regular host reaction to injury or infection caused by toxic factors, pathogens, damaged cells, irritants, and allergens. Antiinflammatory peptides (AIPs) are present in all living organisms, and many peptides from herbal, mammalian, bacterial, and marine origins have been shown to have antimicrobial and/or antiinflammatory properties. METHODS: In this study, we investigated the effects of antiinflammatory peptides on inflammation, and highlighted the underlying mechanisms responsible for these effects. RESULTS: In multicellular organisms, including humans, AIPs constitute an essential part of their immune system. In addition, numerous natural and synthetic AIPs are effective immunomodulators and can interfere with signal transduction pathways involved in inflammatory cytokine expression. Among them, some peptides such as antiflammin, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), and those derived from velvet antler proteins, bee venom, horse fly salivary gland, and bovine ß-casein have received considerable attention over the past few years. CONCLUSION: This article presents an overview on the major properties and mechanisms of action associated with AIPs as immunomodulatory, chemotactic, antioxidant, and antimicrobial agents. In addition, the results of various studies dealing with effects of AIPs on numerous classical models of inflammation are reviewed and discussed.

Plant food allergy: Influence of chemicals on plant allergens.

Plant-derived foods are the most common allergenic sources in adulthood. Owing to the rapidly increasing prevalence of plant food allergies in industrialized countries, the environmental factors are suspected to play a key role in development of allergic sensitization. The present article provides an overview of ways by which chemicals may influence the development and severity of allergic reactions to plant foods, with especial focus on plant allergens up-regulated under chemical stress. In plants, a substantial part of allergens have defense-related function and their expression is highly influenced by environmental stress and diseases. Pathogenesis-related proteins (PR) account for about 25% of plant food allergens and some are responsible for extensive cross-reactions between plant-derived foods, pollen and latex allergens. Chemicals released by anthropogenic sources such as agriculture, industrial activities and traffic-related air pollutants are potential drivers of the increasing sensitization to allergenic PRs by elevating their expression and by altering their immunogenicity through post-translational modifications. In addition, some orally-taken chemicals may act as immune adjuvants or directly trigger non-IgE mediated food allergy. Taken together, the current literature provides an overwhelming body of evidence supporting the fact that plant chemical exposure and chemicals in diet may enhance the allergenic properties of certain plant-derived foods.

Candida albicans - Biology, molecular characterization, pathogenicity, and advances in diagnosis and control - An update.

Candida albicans is an emerging multidrug-resistant fungal pathogen representing an important source of invasive disease in humans and generating high healthcare costs worldwide. This fungus is frequently found in different anatomical sites of healthy persons and could induce systemic and superficial infections under optimal environmental conditions. Invasive candidiasis (IC) is an important nosocomial infection with high morbidity and mortality rates in hospitalized children. It represents a major source of prolonged infections in intensive care unit (ICU), particularly in immunosuppressed or elderly patients. Clinical diagnosis of candidiasis could be difficult because of the lack of specific symptoms and clinical signs. Although C. albicans is the most frequently isolated Candida species in IC, non-albicans Candida (NAC) species are also commonly detected. Multilocus enzyme electrophoresis (MLEE), fragment length polymorphism (RFLP), electrophoretic karyotyping (EK), and random amplified polymorphic DNA (RAPD), multilocus sequence typing (MLST) are known as an efficient technique used for molecular typing of Candida species. The efficacy of antifungal treatment against candidiasis has been evaluated and discussed in the context of large epidemiological studies. The present review highlights the etiology, epidemiology, molecular typing, commensalism and virulence factors, along with the appropriate prevention and control strategies regarding this widespread pathogen.

Immunoproteomics of tree of heaven (Ailanthus atltissima) pollen allergens.

Ailanthus altissima pollen (AAP) is considered as an emerging cause of respiratory allergy in United States, Italy and Iran. However, the allergenic composition of AAP is still unknown and has yet to be characterized. The present study aimed to identify AAP allergens using a proteomics-based approach. For this purpose, optimized AAP protein extracts were analyzed using 1D- and 2D- gel electrophoresis and confronted to twenty sera from individuals with respiratory allergy during the AAP season. Candidate allergens were detected using the serum from an allergic patient with clinical history of AAP pollinosis. IgE-binding spots were identified using MALDI-TOF/TOF mass spectrometry and database searching. According to our results, AAP extracts were rich in proteins (up to 16.25mg/ml) with a molecular-weight distribution ranging from 10 to 175kDa. Two-D electrophoresis of AAP extracts revealed 125 protein spots from which 13 were IgE reactive. These IgE-binding proteins were identified as enolase, calreticulin, probable pectate lyase 6, conserved hypothetical protein and ras-related protein RHN1-like. By our knowledge, this study is the first report identifying AAP allergens. These findings will open up further avenues for the diagnosis and immunotherapy of the AAP allergy as well as for the cloning and molecular characterization of relevant allergens. BIOLOGICAL SIGNIFICANCE: Ailanthus altissima colonizes new areas every year in Iran and is spreading aggressively worldwide. According to USDA, the tree of heaven is now present as an invasive plant in 30 states in US (www.invasivespeciesinfo.gov/plants/treeheaven.shtml) and come to dominate large areas in many regions. Up to now, several cases of allergy to A. altissima pollen have been reported in United States, Italy and Iran [1-4]. However, there is still no information on the sensitizing allergens and the molecular origin of these clinical symptoms, which constitutes a serious threat to patients suffering from respiratory allergies in these regions. To our knowledge, the current study describes, therefore, the first panel of proteins responsible for IgE-mediated A. altissima pollinosis by using a gel-based proteomic approach. This work represents the pioneer proteomic investigation on Simaroubaceae spp. and provides useful insights for further studies on the allergens of this widely distributed plant family.