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OBJECTIVES: To compare tuberculosis (TB) screening results before and after implementation of a stratified testing strategy screening pilot, incorporating interferon gamma release assay (IGRA) and tuberculin skin testing (TST), based on country of origin. METHODS: In 2015, the Washington State Department of Corrections began screening people born outside of the U.S. for TB with IGRA, while U.S.-born people continued screening by TST. RESULTS: Of 405 (75%) foreign-born men screened with IGRA, 403 had valid test results and IGRA screening positivity was 10.4% (N=42). In contrast, among 5,940 primarily U.S-born men screened with TST, 24 (0.4%) were positive. Overall positivity was 1.05%, similar to TST-only positivity in 2013 (1.05%) and 2014 (0.85%). CONCLUSIONS: Incorporating IGRA screening among foreign-born persons was feasible in this state prison system.

Introduction. In the context of a decrease in the tension of the epidemic situation on tuberculosis in Russia, it remains relevant to search for new ways to increase the effectiveness of preventive anti-tuberculosis measures among children and teenagers, taking into account an integrated approach to assessing all risk factors for tuberculosis in various age groups of the child population.Objective. Tо study the complex characteristics of groups at increased risk of tuberculosis among children of different ages who have positive results of a skin test with a recombinant tuberculous allergen (АТR).Materials and methods. The study retrospectively included 392 patients aged 2–17 years with a positive ATR test result. The рatients were randomized by age into 3 groups: in the 1st group there were 87 children 2–7 years old, in the 2nd group 182 children aged 8–14 years were included, in the 3rd group included 121 patients 15–17 years. The children did not have clinical and radiological signs of active tuberculosis and were HIV-negativ.Result. Among children and adolescents with a positive result of the test with ATR, social risk factors for developing tuberculosis (unfavorable living conditions, lack of permanent employment in 86.3% of parents) were determined. It was found that children living in families with low social status were dominated by contact with patients with multidrug resistance of the pathogen (MDR-TB), more than half of children (53.1%) had comorbidities. In 13.3% of children, small calcifications were detected in the lungs, in the intrathoracic lymph nodes.Conclusion. Among children 2–7 years old with positive results of the test with ATR, a complex of risk factors for the development of tuberculosis prevails: low material security in every second family, alcohol and drug dependence of parents in every third family, contact with MDR-TB patients in 56.5% of children, high incidence of concomitant pathology (in 67.4% of children).

Objective: Controversies continue over the diagnostic approach, prediction, and premedication in radiocontrast media (RCM) hypersensitivity. One of the most important problems encountered in daily clinical practice is that patients do not recall which contrast agent has been used in previous exposures. Also, in most cases, the details of the reaction have not been recorded. Therefore, difficulties are experienced in decision-making about skin testing and premedication in patients who are suspected of RCM hypersensitivity. To assess the clinical value of skin tests and premedication in RCM hypersensitivity. Materials and Methods: A retrospective evaluation was made of the medical records of patients between October 2014 and December 2019. The skin tests were performed with the culprit agent if it was known, otherwise, with iohexol, one of the most commonly used RCM in Turkey. As premedication, oral methylprednisolone 40 mg 13-7-1 hours before the procedure and oral pheniramine 22.7 mg 1 hour before the procedure were prescribed. Results: A total of 41 patients were evaluated (32 females and 9 males). Of the reactions, 35 (85.4%) were immediate and 6 (14.6%) were non-immediate. Three (7.3%) had a positive intradermal test result. It was determined that 20 patients (17 immediate, 3 non- immediate), required imaging with RCM again. Of these, 18 received premedication and two did not, although it was recommended. Of the patients who received premedication, one (5.5%) had an urticarial reaction of the same grade, while both patients (100%) who did not receive premedication developed an immediate allergic reaction that was of a similar grade to that of the previous reaction. Conclusion: Skin test positivity for RCM was observed at low rates. In cases with negative skin tests and when the culprit drug cannot be identified, re-exposure to alternative RCM under premedication may reduce the risk of the reaction. Keywords: Allergy, iodinated contrast media, iobitridol, iohexol, premedication

International audience; Drug hypersensitivity reactions (DHRs) to intravenous drugs can be severe and might leave patients and doctors in a difficult position where an essential treatment or intervention has to be suspended. Even if virtually any intravenous medication can potentially trigger a life-threatening DHR, chemotherapeutics, biologics, and antibiotics are amongst the intravenous drugs most frequently involved in these reactions. Admittedly, suspending such treatments may negatively impact the survival outcomes or the quality of life of affected patients. Delabeling pathways and rapid drug desensitization (RDD) can help reactive patients stay on first-choice therapies instead of turning to less efficacious, less cost-effective, or more toxic alternatives. However, these are high-complexity and high-risk techniques, which usually need expert teams and allergy-specific techniques (skin testing, in vitro testing, drug provocation testing) to ensure safety, an accurate diagnosis, and personalized management. Unfortunately, there are significant inequalities within and among countries in access to allergy departments with the necessary expertise and resources to offer these techniques and tackle these DHRs optimally. The main objective of this consensus document is to create a great benefit for patients worldwide by aiding allergists to expand the scope of their practice and support them with evidence, data, and experience from leading groups from around the globe. This statement of the Drug Hypersensitivity Committee of the World Allergy Organization (WAO) aims to be a comprehensive practical guide on the technical aspects of implementing acute-onset intravenous hypersensitivity delabeling and RDD for a wide range of drugs. Thus, the manuscript does not only focus on clinical pathways. Instead, it also provides guidance on topics usually left unaddressed, namely, internal validation, continuous quality improvement, creating a healthy multidisciplinary environment, and redesigning care (including a specific supplemental section on a real-life example of how to design a dedicated space that can combine basic and complex diagnostic and therapeutic techniques in allergy).

The practice of food allergy (FA) for clinicians has boomed, with a dramatic rise in the number of patients and families seeking care and with many advances on several fronts. The practice itself sometimes is evidence-based science and sometimes an art of pattern and phenotype recognition. This article examines the tools for diagnosis and management and therapy options available to physicians providing care for patients with FA. The article touches on pressing needs of clinicians and highlights the rapid and important movements in national and international support and advances that will have a positive impact on the field of FA.

Objectives. Sensitization to specific inhalant allergens is a major risk factor for the development of atopic diseases, which impose a major socioeconomic burden and significantly diminish quality of life. However, patterns of inhalant allergic sensitization have yet to be precisely described. Therefore, to enhance the understanding of aeroallergens, we performed a cluster analysis of inhalant allergic sensitization using a computational model.Methods. Skin prick data were collected from 7,504 individuals. A positive skin prick response was defined as an allergen-to-histamine wheal ratio ≥1. To identify the clustering of inhalant allergic sensitization, we performed computational analysis using the four-parameter unified-Richards model.Results. Hierarchical cluster analysis grouped inhalant allergens into three clusters based on the Davies-Bouldin index (0.528): cluster 1 (Dermatophagoides pteronyssinus and Dermatophagoides farinae), cluster 2 (mugwort, cockroach, oak, birch, cat, and dog), and cluster 3 (Alternaria tenus, ragweed, Candida albicans, Kentucky grass, and meadow grass). Computational modeling revealed that each allergen cluster had a different trajectory over the lifespan. Cluster 1 showed a high level (>50%) of sensitization at an early age (before 19 years), followed by a sharp decrease in sensitization. Cluster 2 showed a moderate level (10%–20%) of sensitization before 29 years of age, followed by a steady decrease in sensitization. However, cluster 3 revealed a low level (

Introduction: Allergic and nonallergic hypersensitivity reactions to iodinated contrast media (ICM) and gadolinium-based contrast media are classified as immediate or non-immediate hypersensitivity reactions (IHR and NIHR), respectively. Skin tests and provocation tests are recommended for the evaluation of hypersensitivity reactions to contrast agents; however provocations are not common in clinical practice. Methods: A MEDLINE search was conducted to investigate studies comprising both skin tests and provocation tests that evaluated hypersensitivity reactions to ICM. Results: Nineteen studies were identified that reported on skin tests, followed by provocations. In the case of IHR to ICM, 65/69 (94%) patients with a positive skin test for the culprit media tolerated a challenge with a skin-test-negative alternative ICM. In IHR to ICM with a negative skin test for the culprit media, provocations were positive in 3.2%–9.1% patients. In the case of a NIHR to ICM with a positive skin test, provocation with a skin-test-negative agent was tolerated in 75/105 (71%) of cases. In NIHR with a negative skin test for the culprit agent, re-exposure to the culprit or an alternative was positive in 0%–34.6% patients. Provocations with the same ICM in skin test positive patients with IHR or NIHR were positive for a majority of the patients, although such provocation tests were rarely performed. Data on hypersensitivity reactions, skin tests and provocations with gadolinium-based contrast media were limited; however, they exhibited a pattern similar to that observed in ICM. Conclusion: In both ICM and gadolinium-based contrast media, the risk of an immediate repeat reaction is low when skin tests are negative. In contrast, a provocation with a skin-test-positive contrast medium showed a high risk of an immediate repeat hypersensitivity reaction. Therefore, a thorough medical history is necessary, followed by skin tests. A provocation is recommended, for diagnostic work-up, when the diagnosis is uncertain.

Latent tuberculosis infection (LTBI) is defined as a consistent immune response to Mycobacterium tuberculosis antigens without evidence of clinically evident active tuberculosis (TB). Diagnosis and treatment for LTBI are important for TB, especially in high-risk populations especially in high prevalent country like India. Tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) are used to diagnose LTBI. Therefore an unequivocal policy /of diagnosis and treatment of LTBI will serve to ameliorate the standards of the Indian health scenario and bring the TB infection to the propinquity of its ultimate elimination.

Background China and Spain are world leaders in the consumption of edible bulbs (garlic and onion), but there are few references to their capacity to cause allergic symptoms. The target was to study allergic sensitization and clinical symptoms associated with garlic and onion consumption in a large sample of allergic patients. Methods An observational cross-sectional study was conducted, testing garlic and onion extracts in 8109 patients of all ages seen by our allergy clinic in 2018. Forty-four aeroallergens and foods were tested, including garlic and onion, with prick test and determination of specific IgE. Oral provocation and contact tests were performed if a delayed reaction was suspected. Western Blot was performed in the serum of patients positive to garlic and onion. Results We conducted 356,798 skin tests and 4254 specific IgE determinations. Of the 8109 patients tested, 2508 (30.92%) presented with symptoms associated with food intake and, in these patients, food hypersensitivity was detected by skin test, positive specific IgE or provocation in 924 patients, and was caused by garlic or onions in 27, indicating a prevalence of 2.92%. Immunodetection showed an association between the symptoms and a specific LTP to these bulbs, without cross-reactivity with other LTPs in the Mediterranean diet (peach, wheat). Conclusions Allergic hypersensitivity to garlic and onions should not be underestimated and, given their high consumption, should be included in the diagnostic food allergy battery.

The persistence of new leprosy cases in endemic areas such as India, Brazil, Bangladesh, and the Philippines has encouraged studies of chemoprophylaxis among contacts of patients. Epidemiological screening tools to enable early detection of infected individuals in endemic populations would be critical to target individuals most in need of intervention. Despite decades of attempts, however, there still are no tests available for the early detection of low-level infection with Mycobacterium leprae. In this report, we describe the development of a leprosy skin test using M. leprae-specific antigens. We selected the chimeric LID-1 fusion protein, formulated to achieve maximum performance at a minimal dose, as a skin test candidate based on its ability to elicit delayed-type hypersensitivity (DTH) reactions in M. leprae immune guinea pigs in a sensitive and specific manner, i.e., with no cross-reactivity observed with other mycobacterial species. Importantly, evaluations in armadillos indicated that intradermal inoculation of formulated LID-1 could distinguish uninfected from M. leprae-infected animals manifesting with symptoms distinctly similar to the PB presentation of patients. Together, our data provide strong proof-of-concept for developing an antigen-specific skin test to detect low-level M. leprae infection. Such a test could, when applied with appropriate use of chemo- and/or immunoprophylaxis, be instrumental in altering the evolution of clinical disease and M. leprae transmission, thus furthering the objective of zero leprosy.

The aim of the study was to evaluate the diagnostic parameters of various methods for determining sensitization to rye allergen in patients with respiratory allergic diseases — allergic rhinitis and bronchial asthma.Material and methods. In the study, 88 patients with allergic rhinitis and/or atopic asthma were examined with three different methods of specific allergic diagnosis (in vivo and in vitro). Inclusion criteria were a diagnosis of allergic rhinitis (both intermittent and persistent) and/or atopic asthma. The pre-test was conducted according to the classic test method according to the normative documents with commercial allergen extracts. Western blots for the determination of IgE levels were performed using RIDA AllergyScreen test systems (R-Biopharm AG, Darmstadt, Germany) and Euroline (Euroimmun).Results. The results of the two systems for the determination of specific IgE for rye allergen by the Rida AllergyScreen and Euroline methods are not in good agreement due to the significant systematic divergence of indicators. The systematic error of the measurement results is 2.6 ku/l, which indicates the presence of a systematic difference. The distribution graph corresponds to the type of absolute systematic error graphs. The standard deviation of the differences was 8.1, which is significantly compared to the values themselves; there is no dependence of the measurement difference on the amount of specific IgE in the blood.Conclusions. The results of the two systems for the determination of specific IgE for rye allergen by the Rida AllergyScreen and Euroline methods are not in good agreement due to the significant systematic divergence of indicators. Between skin test with rye allergens and detection of specific IgE by the Rida AllergyScreen method there is a moderate agreement between study results, between skin test with rye allergen and detection of specific IgE by the Euroline method there is moderate agreement between test results.

Background A large proportion of cow's milk (CM)-allergic children are able to tolerate extensively heated forms of CM such as baked goods. Little is known about whether ultra-heat-treated (UHT) forms of cow's milk are immunologically similar to extensively heated cow's milk and therefore may be tolerated by these children. Objective To determine whether skin test wheal size using UHT CM was significantly different from other forms of CM and CM extracts. Methods Children presenting for oral food challenges with either extensively heated or unheated cow's milk underwent skin prick test (SPT) to commercial CM, UHT CM, evaporated CM, and fresh whole CM. The results were compared between groups of children. Results At study exit, only 14% of children were avoiding all forms of CM, compared with 70% at study entry. No difference was seen in the mean SPT results for UHT CM between those children that could tolerate heated CM compared with those that could not. The mean SPT result for casein was significantly lower in those that could tolerate heated CM. However, within the group of heated milk–tolerant children, the mean SPT for UHT CM was significantly lower than the SPT for fresh whole CM. Conclusion Ultra-heat-treated CM does not behave significantly differently from other forms of CM when evaluated by SPT in heated milk–allergic vs heated milk–tolerant children. This suggests that UHT CM is not sufficiently immunologically different from unheated CM to be tolerated by heated CM–tolerant children.

Background: Allergic bronchopulmonary aspergillosis ABPA is an unusual but not rare illness that affects young atopic adults with allergic asthma. There are clinical and laboratory tests for the diagnosis of ABPA, these tests include history of asthma, peripheral blood eosinophilia, immediate cutaneous reactivity to Aspergillus fumigatus, serum precipitating antibodies to A. fumigatus or elevated total serum IgE and radiological infiltration. Objectives: This is a case control study designed to evaluate the frequency ofallergic bronchopulmonary aspergillosis ABPAin patients with asthma. Methods: This is a case control study carried on 150 asthmatic patients consulting the allergic disease center of Aljumhori Teaching Hospital in Mosul for the period from November 2003 to July 2004 to identify patients with allergic bronchopulmonary aspergillosis ABPA. Their ages ranged from 6-65 years, 52% of them were females and 48% were males. The results were compared with a 60 apparently healthy individuals selected randomly as a control group. To prove that patients’ symptoms were allergic bronchopulmonary aspergillosis ABPA, the following tests were performed for all patients, peripheral eosinophilia which was found in 40.6% of asthmatic patients, skin test for Aspergillus which was positive in 51.3%, ELISA test for total IgE which was positive in 28% and chest-X ray abnormalities were found in 17.3% of patients mainly as pulmonary infiltration. Results:The major criteria for allergic bronchopulmonary aspergillosis ABPA were found in 19(12.6%) patients out of 150. Moreover, it was significantly higher in most age groups mainly in those patients between 6-15 years and 16-25 years of age. Peripheral eosinophilia, Skin test, ELISA and CXR did not appear to be related to the sex of patients or duration of asthma, but they were significantly higher than the control group (PConclusion:The current study revealed that 12.6% of asthmatic patients fulfill the criteria of allergic bronchopulmonary aspergillosis ABPA and there was a significant relationship between asthma and Aspergillus fumigatus as a risk factor.

Background The diagnostic approach for beta-lactam (BL) drug hypersensitivity reactions (DHR) is based on the history, clinical signs, skin tests (ST), in vitro tests, and drug provocation tests (DPT). The aim of this study was to assess the performance of an allergy workup with ST in a real-world use. Methods In this cross-sectional study the rate of positive ST in subjects with suspected DHR to penicillins and cephalosporins was investigated. Of special interest were correlations of ST positivity: 1) to the time intervals between index reaction and the allergic work-up, 2) time interval from drug exposure to the onset of signs, 3) pattern of manifestation in delayed DHR and involvement of test area in the index reaction, and 4) potential advantage of patch testing in delayed DHR. Results 175 patients were included between January 2018 and April 2019 (63.4% female), 45 (25.7%) with immediate DHR manifestation and 130 with delayed DHR manifestation (74.3%). A total of 44 patients (25.1%) had a positive ST (immediate DHR 37.8% versus 20.0% in delayed DHR). ST positivity decreased in both groups after 3 years from 47.8% [95%CI 29.2–67] to 23.5% [95%CI 9.6–47.3] in immediate DHR and 23.0% [95%CI 15-4-32.9] to 12.9% [95%CI 5.1–28.9] in delayed DHR. The proportion of positive ST was higher in patients with more severe forms of delayed DHR, and in subjects with a shorter latency period of onset of symptoms after drug exposure: 0-3d: 29.5% [95%CI 19.6–41.9] vs. >3d: 11.6% [95%CI 6.0–21.2]). No sensitization was shown in delayed urticaria or angioedema. ST done outside the skin area involved during the index reaction were negative in all cases (0/38 vs. 26/84 in cases with involved area). The combination of patch test and intradermal test (IDT) revealed an additional positive result in 2/77 cases. Additional in vitro testing reduced the proportion of negative test results to 72%. Conclusion In most patients with negative test results, we could not clarify the cause of the BL-associated adverse events even with further investigations (including DPT). How to prevent new drug-induced adverse events in such patients has hardly been investigated yet. Corresponding cohort studies could improve the data situation.

Allergies to gadolinium-based contrast agents (GBCAs) are rare and manifest usually as an immediate drug hypersensitivity reaction (DHR), compatible with an immunoglobulin E (IgE)-mediated mechanism. Although the molecular structures of GBCA show some similarities and are either linear or macrocyclic, the frequency and pattern of cross-reactivity remain unclear. However, cross-reactivity has been described. The aim of this investigation was to assess cross-reactivity in patients with GBCA allergy based on skin tests and exposure. We retrospectively evaluated a total of 28 cases with a proven allergy to a GBCA, including 11 from the database of the allergy division of the Inselspital, Bern and 17 published cases from the literature, retrieved with a PubMed-MEDLINE search. The majority of cases were immediate DHR, with 8/11 cases from the database (72.7%) and 16/17 published cases (94.1%). In both groups macrocyclic GBCA were most often identified as causative drugs. A cross-reactivity based on skin test results was found in 2 out of 11 database cases (18.2%) and in 6 out of 17 literature cases (35.3%). Cross-reactivity occurred within macrocyclic GBCA in 1/11 database cases and 3/17 literature cases, and included both macrocyclic and linear GBCA in 1/11 and 4/17 subjects. There was no cross sensitization among linear GBCA. Skin test-negative GBCA were well tolerated, even in cases with sensitization to linear and macrocyclic GBCA. Overall, cross-reactivity in GBCA allergy is rare (approximately 29%), and may occur among macrocyclic GBCA or in between macrocyclic and linear GBCA. IgE to linear GBCA seems to be rarely cross-reactive. Skin test is helpful in identifying safe alternatives, as no reaction to skin test-negative GBCA was observed.

Eighty-six clinically normal adult dogs from southern Florida, USA, with no history of dermatitis, were intradermally skin tested with Greer flea antigen 1:1000 w/v to determine the prevalence of positive immediate intradermal reactivity. This study describes the test group of animals and reports the prevalence of sensitivity to the Greer whole-body flea antigen in normal dogs living in a flea-rich environment. Similar to previous research, the highest prevalence of reactivity to flea antigen occurred at 3-4 years of age. The results indicate that 24% of clinically normal dogs from a flea-rich environment exhibited positive immediate skin test reactivity. These dogs had no clinical signs of flea allergic dermatitis (FAD) in spite of ongoing flea exposure. A 2-year follow-up telephone call to the owners of these flea antigen intradermal skin test (IDST)-positive dogs indicated that only two of 21 dogs had developed clinical signs of FAD.

In this review, we outline and reflect on the important differences between allergen-specific immunotherapy for inhalant allergies (i.e., aeroallergens) and venom-specific immunotherapy (VIT), with a special focus on Venomil® Bee and Wasp. Venomil® is provided as a freeze-dried extract and a diluent to prepare a solution for injection for the treatment of patients with IgE-mediated allergies to bee and/or wasp venom and for evaluating the degree of sensitivity in a skin test. While the materials that make up the product have not changed, the suppliers of raw materials have changed over the years. Here, we consolidate relevant historical safety and efficacy studies that used products from shared manufacture supply profiles, i.e., products from Bayer or Hollister–Stier. We also consider the characterization and standardization of venom marker allergens, providing insights into manufacturing controls that have produced stable and consistent quality profiles over many years. Quality differences between products and their impacts on treatment outcomes have been a current topic of discussion and further research. Finally, we review the considerations surrounding the choice of depot adjuvant most suitable to augmenting VIT.

The leishmanin skin test (LST) has been used for decades to detect exposure and immunity to the parasiteLeishmania, the causative agent of the neglected tropical disease leishmaniasis. In the LST,Leishmaniaantigen (leishmanin) is intradermally injected into the forearm. In an individual who has been previously infected, a delayed-type hypersensitivity (DTH) reaction results in a measurable induration at the site of the injection, indicating that previous exposure toLeishmaniahas resulted in the development of cell-mediated immunity. LST positivity is associated with long-lasting protective immunity against reinfection, most notably as reported for visceral leishmaniasis (VL). Despite efforts over the past few decades, leishmanin antigen is no longer produced under good manufacturing practice (GMP) conditions anywhere in the world. Consequently, the use of the LST in epidemiological studies has declined in favor of serological and molecular tests. In this review, we provide a historical overview of the LST and justification for the reintroduction of leishmanin. A GMP-grade leishmanin can be used to detect immunity in vivo by the LST and can be investigated for use in an interferon-γ release assay (IGRA), which may serve as an in vitro version of the LST. The LST will be a valuable tool for surveillance and epidemiological studies in support of the VL elimination programs and as a surrogate marker of immunity in vaccine clinical trials.MethodsA review of the literature was conducted using PubMed as the primary database, with MeSH terms “leishmanin skin test” OR “Montenegro test” OR “Montenegro skin test.” Articles written in English that describe the history or standardization of leishmanin, the use of leishmanin in an IGRA, or the use of the LST in epidemiological studies or vaccine trials were prioritized in our appraisal of the literature.

Introduction. Current intradermal tuberculin skin tests for latent tuberculosis infection (LTBI) based on purified protein derivative (PPD) have poor specificity.Aims. Developing a better skin test antigen as well as a simple skin patch test may improve and facilitate diagnostic performance.Methodology. Defined recombinant antigens that were unique to Mycobacterium tuberculosis (MTB), including two potential latency-associated antigens (ESAT-6 and Rv2653c) and five DosR-encoded latency proteins (Rv1996, Rv2031c, Rv2032, DevR and Rv3716c), were used as diagnostic skin test reagents in comparison with a standard PPD. The performance of the skin tests based on the detection of delayed-type hypersensitivity (DTH) reaction in guinea pigs sensitized to MTB and M. bovis bacille Calmette-Guerin (BCG) vaccine was evaluated.Results. The latency antigens Rv1996, Rv2031c, Rv2032 and Rv2653c and the ESAT-6 protein elicited less reactive DTH skin responses in MTB-sensitized guinea pigs than those resulting from PPD, but elicited no response in BCG-vaccinated guinea pigs. The remaining two latency antigens (DevR and Rv3716c) elicited DTH responses in both groups of animals, as did PPD. The reactivity of PPD in BCG-vaccinated guinea pigs was greater than that of any of the selected skin test reagents. Using stronger concentrations of selected skin test reagents in the patch test led to increased DTH responses that were comparable to those elicited by PPD in guinea pigs sensitized with MTB.Conclusion. Transdermal application of defined purified antigens might be a promising method for LTBI screening.

Background Large local reaction to Hymenoptera stings is usually defined as a swelling >10 cm which lasts longer than 24 hours, sometimes associated with erythema, pruritus and blisters. Currently, the risk of subsequent systemic reactions after re-stings is considered low (2%-15%). Therefore, a diagnostic workup in case of large local reaction is often judged unnecessary, as well as adrenaline auto-injector and venom immunotherapy prescription. The aim of this study was to prospectively evaluate the outcome of re-stings in a real-world setting, in patients with a history of one previous large local reaction. Methods We consecutively enrolled patients who experienced their first large local reaction (as per EAACI definition), treated with antihistamine and steroids. They were followed for field re-stings and assessed for risk of subsequent systemic reactions. Results We enrolled 662 patients. Out of the 225 re-stung subjects, 24% did not experience reactions, 52% reported a second large local reaction and 24% had systemic reactions. The risk of subsequent systemic reactions was higher in case of skin test reactivity to Apis mellifera or Vespula species (OR 2.1 and 3.8, respectively), in particular if positive at 0.001 µg/mL concentration (OR 13.4 and 16.5, respectively). Conclusions Systemic reactions, after a previous large local reaction, occur more frequently than that reported by literature. After analysing the predictive role of large local reactions for systemic reactions, we demonstrated that an accurate diagnostic workup may be considered, particularly skin tests. Further studies in different countries are needed to confirm these results and large local reaction management.

The article assesses existing immunological tests aimed to detect tuberculosis infection (tuberculin skin test, IGRA, skin test with a recombinant tuberculosis allergen). The latest inventions in the development of immunological tests that can differentiate latent tuberculosis infection and active tuberculosis have been analyzed. The difficulties encountered when developing such a test and conducting clinical trials have been demonstrated. The article presents the experience of the Moscow TB service in using the skin test with recombinant tuberculosis allergen as a screening method for tuberculosis infection, its ability to detect the infection at the stage of its development when preventive therapy is most effective since anti-tuberculosis drugs kill mycobacteria that are replicating but not dormant. Such tactics contributed to the incidence rate decrease both in high-risk groups and among the general population.

This prospective cohort study was conducted to compare the accuracy of QuantiFERON®-TB (QFT) Gold In-Tube test and tuberculin skin test (TST) in diagnosing tuberculosis (TB) in predominantly bacille Calmette-Guerin-vaccinated children with a high incidence of malnutrition. The sensitivity of the QFT versus the TST was 69.6% versus 52.9% for WHO-defined TB, with specificity of 86% versus 78.3%, respectively. The concordance of the TST and QFT was 79% overall (κ = 0.430), 62.5% in those with WHO-defined TB and 85.7% in those without TB. Majority of the QFT+/TST - discordance was seen in children with TB, whereas majority of the TST+/QFT - discordance was seen in those without TB. The TST was more likely to be negative in children with moderate-to-severe malnutrition (P = 0.003) compared to the QFT, which was more likely to be positive in younger children. The significantly better performance of the QFT in malnourished children and those at younger ages supports its use for TB diagnosis in these subpopulations.

Chronic spontaneous urticaria (CSU) is a chronic type characterized by episodes of wheals with or without angioedema. Autoantibody against the alpha subunit of Fc epsilon receptor (FcεRIa) was detected in CSU patients' sera. The study aims to evaluate the clinical utility of skin tests in CSU patients. In addition, it assesses the presence of circulating FcεRIa in CSU patients and their correlation with other clinical and immunological variables. The study includes 40 healthy controls and 40 CSU patients who had urticaria symptoms for at least 8 weeks. All subjects underwent the following tests: autologous serum skin test (ASST), autologous plasma skin test (APST), immunoglobulin E (IgE), antinuclear antibodies (ANA), antithyroid antibodies (ATA). An in-house enzyme-linked immunosorbent assay was used for FcεRIa detection. The prevalence of ANA and ATA in CSU was 7.5% and 20% respectively. Total IgE was significantly higher in CSU than in controls (p 0.0001). The study detected circulating antibody to FcεRIα in 2.5% of controls and 52.5% of CSU patients (p 0.0001). The prevalence of antibody to FcεRIa was 27.3% and 83.3% of ASST negative and positive patients respectively (p = 0.0004). But the prevalence was 17.6% and 78.3% of APST negative and positive patients respectively (p = 0.0002). In conclusion, Circulating antibody to FcεRIa has a role in the pathogenic mechanisms of CSU.

La campagne vaccinale contre la Covid-19 a été marquée par une grande appréhension vis-à-vis du risque allergique, en particulier vis-à-vis des excipients vaccinaux : polyéthylène glycol (PEG), polysorbate ou encore trométamol. Une allergie confirmée à ces derniers ou après la première dose de vaccin constitue une contre-indication vaccinale. Nous rapportons le cas d’un patient présentant une allergie avérée au PEG et une sensibilisation cutanée au vaccin COMIRNATY® (PEG dans sa composition). Il a pu bénéficier de ce vaccin dans le cadre d’un protocole d’induction de tolérance en 5 étapes. Conclusions : une prise en charge allergologique spécifique doit être proposée aux patients suspects d’hypersensibilité sévère au PEG ou à d’autres excipients vaccinaux. Nous proposons ici un protocole ayant permis, sur un cas d’allergie avérée au PEG, d’administrer le vaccin COMIRNATY® sans réaction secondaire.

Before the initiation of biotherapy in the treatment of rheumatic diseases, it is highly recommended for the patients to be screened for latent tuberculosis infection (LTBI). The objective of this study is to identify the prevalence of LTBI among patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) before the initiation of biologic therapy in the Moroccan biotherapy registry (RBSMR). A cross sectional study was conducted using the baseline data of the Moroccan biotherapy registry. Tuberculin skin test or IGRA test or both tests were done before starting anti-TNF treatment for screening LTBI. The comparisons between positive and negative LTBI patients according to rheumatic disease were examined using categorical comparisons. 259 patients were included in this study.94 patients had RA and 165 had SpA. The mean age of the RA patients was 50.49 ± 11.82 years with a majority of females (84%). The mean age for the SpA patients was 36 ± 13.7 years with a majority of males (67.3%). The prevalence of LTBI in the RBSMR was 21.6%. This prevalence was at 24.8% in SpA patients, while it was at 15.9% for RA patients. After the comparison between positive and negative LTBI patients according to rheumatic disease, no demographic, clinical, or therapeutic characteristics were statistically associated with LTBI. This study found that in an endemic TB country like Morocco, a high prevalence of patients with SpA and RA had LTBI, and that RA patients had a lower prevalence than SpA patients.

In people who have been vaccinated with Bacillus Calmette-Guérin, the interferon gamma release assay appears to be related to fewer diagnoses for latent tuberculosis infection, fewer prescriptions of preventive tuberculosis therapy, and no difference in the number of active TB cases compared to the tuberculin skin test (findings based on 1 [non-randomized study] of low quality). No evidence-based guidelines were found regarding the identification of latent tuberculosis infection in people with previous Bacillus Calmette-Guérin vaccination.

Reports about cases of anaphylaxis to mRNA vaccines have created anxiety in the community and could increase vaccine hesitancy in the population. There are no standardized protocols for allergy testing to mRNA vaccines. PEG is currently the only excipient in both vaccines with recognized allergenic potential. Allergy to PEG has been reported with increasing frequency over recent years, often in patients who had repeated systemic allergic reactions/anaphylaxis to several classes of drugs before diagnosis. Proposed protocols are based on current knowledge about potential mechanisms of anaphylaxis associated with the mRNA vaccines, and the assumption that polyethylene glycol (PEG) is the most likely culprit. Allergy testing to PEGs and mRNA vaccines is complex and carries the risk of anaphylaxis and should be conducted in a specialist drug allergy center. Appropriate PEG-free emergency medical treatment and supervision should be readily available.

The consumption of quinolones as first-line treatment has increased in recent years, leading to an increase in the incidence of hypersensitivity reactions (HSRs) to this antibiotic group. Both diagnosis and management of HSRs to quinolones are complex and controversial. These practical guidelines aim to provide recommendations for effective clinical practice. The recommendations were drafted by an expert panel that reviewed the literature regarding HSRs to quinolones and analyzed controversies in this area. Most HSRs to quinolones are immediate and severe. The risk for HSRs is higher in patients who report allergy to ß-lactams, moxifloxacininduced anaphylaxis, and immediate reactions than in patients who report reactions to quinolones inducing other symptoms. The usefulness of skin tests in diagnosing HSRs to quinolones is controversial, with sensitivity and specificity varying between studies. Most in vitro tests are produced in-house, with no validated commercial options. The basophil activation test has proven useful for diagnosing immediate reactions, albeit with diverse results regarding sensitivity. Drug provocation testing is currently the gold standard for confirming or excluding the diagnosis and for finding safe alternatives, although it is contraindicated in patients with severe reactions. Cross-reactivity between quinolones has proven controversial in several studies, with the lowest cross-reactivity reported for levofloxacin. Desensitization may be considered in allergy to quinolones when no other alternatives are available.

BackgroundOnly the tuberculin skin test (TST) and two interferon-γ release assays (IGRAs), QuantiFERON-TB Gold In-Tube and T-SPOT.TB, are currently endorsed by the World Health Organization as tests for tuberculosis (TB) infection. While IGRAs are more specific than the TST, they require sophisticated laboratory infrastructure and are costly to perform. However, both types of tests have limited performance to predict development of active TB. Tests with improved predictive performance and operational characteristics are needed.MethodsWe reviewed the current landscape of tests for TB infection identified through a web-based survey targeting diagnostic manufacturers globally.ResultsWe identified 20 tests for TB infection: 15 in vitro tests and five skin tests. 13 of the in vitro tests are whole-blood IGRAs and 14 use early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), with or without additional antigens. 10 of the tests are based on assays other than an ELISA, such as a fluorescent lateral flow assay that requires less manual operation and shorter assay time and hence is more suitable for decentralisation compared with the existing IGRAs. Four of the five skin tests use ESAT-6 and CFP-10 proteins, while the remaining test uses a new antigen that is specific to Mycobacterium tuberculosis complex.ConclusionsNew tests have the potential to improve accuracy, operational characteristics and end-user access to tests for TB infection. However, published data in various populations and settings are limited for most new tests. Evaluation of these new tests in a standardised design would facilitate their endorsement and programmatic scale-up.

Background: Several studies have shown an association between severe asthma and serum immunoglobulins E (IgE) against Staphylococcus aureus enterotoxins (SEs). SEs—the prototypes being types A (SEA), B (SEB) and toxic shock syndrome toxin 1 (TSST-1)—can induce both polyclonal and specific IgE responses. Objective: The aim of the study was to evaluate the ability of SEs to induce basophil activation in severe asthmatic patients using the basophil activation test (BAT). Methods: 57 severe asthmatic patients were enrolled. BAT in response to SEA, SEB and TSST-1 was performed in all patients, while serum IgE to SEA, SEB and SEC was available in 49 patients. BAT was considered positive when CD203c+ basophils to SEs were ≥5%, and the stimulation index (SI, ratio between % of CD203c+ basophils to SEs and to negative control) was >2. Two threshold values (>0.1kU/L and >0.35kU/L, respectively) were used to assess serum SEsIgE. Results: 36.8% of severe asthmatic patients had a BAT positive for at least one SE (BAT SEs+). Serum SEsIgE >0.35kU/L (SEs IgE+) was associated with BAT SEs positivity. Among patients with negative skin prick test, 35% were BAT SEs+, 30% SEs IgE+, 55% BAT or IgE− SEs+. A negative correlation between SI of BAT to SEs and both clinical (ACT score) and functional parameters was observed, together with a positive correlation of BAT with asthma exacerbations. Conclusions: The positivity of BAT for SEs in a subgroup of severe asthmatic patients further supports the pathogenic role of Staphylococcus aureus in severe asthma.

Background The tuberculin skin test (TST) identifies individuals at high risk of developing tuberculosis (TB) but poses many challenges. The blood monocyte-to-lymphocyte ratio (MLR) could be an alternative, as extremes in MLR have been associated with increased risk of TB disease. Methods At a primary care clinic in Johannesburg, a differential white blood cell count and TST was performed in adults starting antiretroviral treatment (ART) without symptoms suggestive of active TB. Results Of 259 participants, 171 had valid results of whom 30% (51/171) were TST positive and the median MLR was 0.18 (IQR 0.13–0.28). The MLR distribution differed between CD4 count categories (p < 0.01), with a broader range of values in TST negative participants with a low CD4 count (≤ 250 cells/mm3), likely reflecting HIV immunosuppression. MLR was associated with a positive TST (OR 0.78 per 0.1 increase, 95% CI 0.59, 0.97) in bivariate analysis but not in multivariate regression analysis (aOR 0.83 for every 0.1 increase, 95% CI 0.60, 1.08). Conclusion In ART-naïve adults without symptoms suggestive of active TB, MLR was not independently associated with TST positivity and is thus unlikely to be a useful alternative to TST. Future research should focus on development of a cheap, simple and accurate biomarker to identify those people benefiting most from preventive TB therapy.

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) can be a severe and debilitating disease associated with significant morbidity, loss of smell, sinus pressure and asthma exacerbations. Eosinophils play a role in the majority (85%) of patients. Benralizumab, an afucosylated monoclonal antibody directed against the IL-5 receptor, has powerful apoptotic effects on eosinophils. Objective We sought to investigate the therapeutic benefit of inhibiting the IL-5 receptor using benralizumab to treat severe rhinosinusitis with nasal polyps. Methods Patients with severe NP (defined by endoscopic grade 5 or more out of 8) with elevated eosinophils and a history of previous surgical or endoscopic polypectomy met entry criteria and were randomized in a double-blind fashion to receive 30 mg benralizumab SC or placebo. Endoscopic NP score was assessed at baseline and at treatment week 20. CT scan, SNOT-22 survey and UPSIT smell test score changes were also evaluated. Results Thirty-three patients were screened, and twenty-four (n = 24) were enrolled in the study. Compared with baseline, benralizumab significantly improved NP score (-0.9 ± 0.2, P = 0.004) whereas placebo did not (-0.3 ± 0.3, P = 0.166). Benralizumab induced polyp size reduction compared with placebo did not reach statistical significance (P = 0.103). Five of 12 benralizumab-treated patients (42%) had improvements in all major outcomes (polyp score, CT, SNOT-22 and smell test) versus 2 out of 12 placebo (17%). The ratio of blood eosinophil count to allergen skin test positivity correlated with polyp reduction. Conclusion Benralizumab was well-tolerated and compared with baseline achieved a statistically significant reduction in nasal polyp size, sinus occupancy, symptoms and improved sensation of smell for most patients (83%).

Summary Tuberculosis (TB) kills more people than any other single infectious disease globally. Despite decades of research, there is no vaccine to prevent TB transmission. Bacille Calmette–Guérin (BCG) vaccine, developed a century ago, is effective against childhood (disseminated and miliary) TB. However, its protective efficacy against pulmonary TB varies from 0 to 80% in different populations. One of the main reasons for the lack of an effective vaccine against TB is the lack of complete understanding about correlates of protective immunity on which to base vaccine design and development. However, some household contacts who are extensively exposed to Mtb infection remain persistently negative to tuberculin skin test and interferon-gamma assay. These individuals, called ‘resisters’, clear Mtb infection early before the development of acquired immunity. The immunological basis of early Mtb clearance is yet to be established; however, innate lymphocytes such as monocytes/macrophages, dendritic cells, neutrophils and natural killer cells, and innate-like T cells such as mucosal-associated invariant T cells, invariant natural killer (NK) T cells and gamma-delta (γδ) T cells, have been implicated in this early protection. In recent years, NK cells have attracted increasing attention because of their role in controlling Mtb infection. Emerging data from animal and epidemiological studies indicate that NK cells play a significant role in the fight against Mtb. NK cells express various surface markers to recognize and kill both Mtb and Mtb-infected cells. This review presents recent advances in our understanding of NK cells in the fight against Mtb early during infection, with emphasis on cohort studies.

In most low- and middle-income countries (LMICs), bovine tuberculosis (bTB) remains endemic due to the absence of control programs. This is because successful bTB control and eradication programs have relied on test-and-slaughter strategies that are socioeconomically unfeasible in LMICs. While Bacillus Calmette-Guerin (BCG) vaccine-induced protection for cattle has long been documented in experimental and field trials, its use in control programs has been precluded by the inability to differentiate BCG-vaccinated from naturally infected animals using the OIE-prescribed purified protein derivative (PPD)-based tuberculin skin tests. In the current study, the diagnostic specificity and capability for differentiating infected from vaccinated animals (DIVA) of a novel defined antigen skin test (DST) in BCG-vaccinated (Bos taurus ssp. taurus x B. t. ssp. indicus) calves was compared with the performance of traditional PPD-tuberculin in both the skin test and in vitro interferon-gamma release assay (IGRA). The IFN- production from whole blood cells stimulated with both PPDs increased significantly from the 0-week baseline levels, while DST induced no measurable IFN- production in BCG-vaccinated calves. None of the 15 BCG-vaccinated calves were reactive with the DST skin test (100% specificity; one-tailed lower 95% CI: 82). In contrast, 10 of 15 BCG-vaccinated calves were classified as reactors with the PPD-based single intradermal test (SIT) (specificity in vaccinated animals = 33%; 95% CI: 12, 62). Taken together, the results provide strong evidence that the DST is highly specific and enables DIVA capability in both skin and IGRA assay format, thereby enabling the implementation of BCG-vaccine based bTB control, particularly in settings where test and slaughter remains unfeasible.

Latent tuberculosis infection (LTBI) is a subclinical mycobacterial infection defined on the basis of cellular immune response to mycobacterial antigens. The tuberculin skin test (TST) and the interferon gamma release assay (IGRA) are currently used to establish the diagnosis of LTB. However, neither TST nor IGRA is useful to discriminate between active and latent tuberculosis. Moreover, these tests cannot be used to predict whether an individual with LTBI will develop active tuberculosis (TB) or whether therapy for LTBI could be effective to decrease the risk of developing active TB. Therefore, in this article, we review current approaches and some efforts to identify an immunological marker that could be useful in distinguishing LTBI from TB and in evaluating the effectiveness of treatment of LTB on the risk of progression to active TB.

Background Paracetamol, a non-steroidal anti-inflammatory drug, is commonly being used for fever and pain relief worldwide. The aim of this study was to evaluate children with a suspected history of paracetamol hypersensitivity. Methods Sixty patients who were referred to our clinic in between January 2015 and December 2018 with a suspected history of paracetamol hypersensitivity were included. Reactions were classified according to the European Network for Drug Allergy (ENDA)/Global Allergy and Asthma European Network classification and European Academy of Allergy and Clinical Immunology (EAACI)/ENDA Position Paper. Diagnoses were confirmed by skin tests and oral challenge tests (OCTs). In those with verified paracetamol hypersensitivity, an OCT with a strong COX-1 inhibitor was performed to classify the type of the reaction to refer as either selective or cross-intolerance hypersensitivity. A subsequent OCT with a selective COX-2 inhibitor was performed in those cross-intolerant patients to find out a safe alternative drug. Results Sixty OCTs with paracetamol were performed to patients with a median age of 8.5 years, and hypersensitivity to paracetamol was verified in 8 patients. Four children were classified as selective responders, and 3 were classified as cross-intolerant after OCT with a COX-1 inhibitor. Overall, skin test positivity for paracetamol was detected in only one patient, in whom OCT with paracetamol was negative. In all 3 cross-intolerant patients, a safe alternative non-steroidal anti-inflammatory drug was identified after an OCT with a selective COX-2 inhibitor. Conclusion OCT stands as the gold-standard procedure in verifying the diagnosis of patients with paracetamol-induced drug hypersensitivity, as well as, in defining the type of reactions and finding out safe alternative drugs.

In 2018, Brazilian guidelines changed to recommend tuberculosis (TB) preventive therapy for all people with HIV and a CD4 cell count 350 cells/μl or less, but only for those with a positive tuberculin skin test (TST) if CD4 cell count is than 350 cells/μl. We determined the potential effectiveness of CD4-based guidelines for TB testing and preventive therapy.Secondary analysis of the stepped-wedge, cluster-randomized THRio trial for isoniazid preventive therapy (IPT).We analyzed data from 4114 newly registered patients with HIV in 29 clinics followed until TB diagnosis, death, or administrative censoring. We compared incidence rates of TB and TB/death between CD4, TST, IPT, and antiretroviral therapy categories.Initial CD4 cell count was 350 cells/μl or less in 2138 (52%) and more than 350 cells/μl in 1976 (48%) patients. TST was performed for 2922 (71%), of whom 657 (16%) were TST-positive [278 (13%) CD4 ≤ 350 vs. 379 (19%) CD4 350]. A total of 619 (15%) received IPT and 2806 (68%) received antiretroviral therapy. For patients with CD4 cell count 350 cells/μl or less who did not receive IPT, the incidence rate of TB was 1.79/100 person-years (pys) and TB/death was 3.89/100 pys. For patients with CD4 cell count more than 350 who did not receive IPT, the incidence rates of TB and TB/death were 0.57/100 and 1.49/100 pys for TST-negatives, and 1.05/100 and 1.64/100 pys for TST-unknowns.TB incidence was high among all patients who did not receive IPT, including those with CD4 cell count more than 350 cells/μl and negative or unknown TST results. TB preventive therapy should be provided to all people living with HIV in medium burden settings, regardless of CD4 cell count and TST status.