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Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The SARS-CoV-2 epidemic has unquestionably left a significant mark on the global healthcare system. Implementation of the commonly available vaccinations against COVID-19 is intended to reduce the risk of a severe course of the disease. Due to a very brief development period of the new vaccines, concerns have appeared among the public with regard to the possible adverse effects of the newly-developed preparations, as well as to the risks of causing allergic reactions. Regular medical observation during the Hymenoptera venom immunotherapy provides significant possibilities to note any potential adverse effects of vaccines against COVID-19, as well as of complications of an experienced SARS CoV-2 infection. Aim: To assess the issues connected with vaccination against COVID-19, complications following vaccination, as well as incidence and course of the disease among patients undergoing venom immunotherapy (VIT) due to an allergy to Hymenoptera venom. Material and methods: We investigated 37 persons aged 19 to 70 (20 women; 17 men) undergoing Hymenoptera venom immunotherapy in our department. Results: 21.6% have experienced an infection with the SARS-CoV-2 virus, confirmed by a diagnostic test. No person participating in the study had experienced a severe infection which would require hospitalization. Elderly people have been vaccinated statistically significantly more often than young people. Conclusions: The risk related to vaccination in this group of patients does not seem to be higher than in the general population. [ABSTRACT FROM AUTHOR]

Background: Clonal mast cell disease (CMD) is an underlying aggravating condition in wasp venom allergy (WVA) which requires a different treatment strategy. CMD is increasingly recognized in patients with normal basal serum tryptase (bsT). However, methods to identify at risk patients have not yet been assessed in large cohorts of WVA patients with normal bsT. Methods: This retrospective study evaluated the reliability of the REMA score in detecting CMD in a cohort of grade IV WVA patients with normal bsT and assessed the added value of other clinical parameters, KIT D816V mutation analysis in peripheral blood (PB) and the diagnosis of hereditary alpha tryptasemia (HAT). All patients had a conclusive bone marrow evaluation that demonstrated or excluded underlying CMD. Results: In total 35 CMD and 96 non‐CMD patients were included. REMA score had a sensitivity of 72% (95% CI 56%–88%) and specificity of 79% (95% CI 70%–87%) in this cohort. Loss of consciousness during systemic reaction and bsT between 6.3 and 11.4 ng/ml were additional parameters independently associated with CMD. Sensitivity of KIT in PB was relatively low, 56% (95% CI 36%–75%), but had added value as screening method in patients with a low REMA score due to 100% specificity. Conclusion: The REMA score is a relatively reliable method to detect patients at risk of CMD among WVA patients with normal bsT. KIT mutation analysis in PB could serve as additional screening method in patients with low REMA scores. [ABSTRACT FROM AUTHOR]

Keywords: allergens; anaphylaxis; IgE; insect venom; nanobodies EN allergens anaphylaxis IgE insect venom nanobodies 2859 2862 4 09/02/22 20220901 NES 220901 For the canonical antibody isotypes, antigen recognition is driven by the variable regions of both heavy and light chains. Nanobody-based human antibody formats act as IgE surrogate in hymenoptera venom allergy Nanobody-based human IgEs (nb-IgEs) were then generated by fusion of obtained allergen-specific nanobodies to the Fc domains of human IgE. [Extracted from the article]

Animal venoms are a rich source of novel biomolecules with potential applications in medicine and agriculture. Ants are one of the most species-rich lineages of venomous animals. However, only a fraction of their biodiversity has been studied so far. Here, we investigated the venom components of two myrmicine (subfamily Myrmicinae) ants: Myrmica rubra and Myrmica ruginodis. We applied a venomics workflow based on proteotranscriptomics and found that the venoms of both species are composed of several protein classes, including venom serine proteases, cysteine-rich secretory protein, antigen 5 and pathogenesis-related 1 (CAP) superfamily proteins, Kunitz-type serine protease inhibitors and venom acid phosphatases. Several of these protein classes are known venom allergens, and for the first time we detected phospholipase A1 in the venom of M. ruginodis. We also identified two novel epidermal growth factor (EGF) family toxins in the M. ruginodis venom proteome and an array of additional EGF-like toxins in the venom gland transcriptomes of both species. These are similar to known toxins from the related myrmicine ant, Manica rubida, and the myrmecine (subfamily Myrmeciinae) Australian red bulldog ant Myrmecia gullosa, and are possibly deployed as weapons in defensive scenarios or to subdue prey. Our work suggests that M.rubra and M. ruginodis venoms contain many enzymes and other high-molecular-weight proteins that cause cell damage. Nevertheless, the presence of EGF-like toxins suggests that myrmicine ants have also recruited smaller peptide components into their venom arsenal. Although little is known about the bioactivity and function of EGF-like toxins, their presence in myrmicine and myrmecine ants suggests they play a key role in the venom systems of the superfamily Formicoidea. Our work adds to the emerging picture of ant venoms as a source of novel bioactive molecules and highlights the need to incorporate such taxa in future venom bioprospecting programs. [ABSTRACT FROM AUTHOR]

Agriculture can benefit from the biotechnological use of animal venom biodiversity. We explored the patent database to find the prevailing applications of scorpion, snake, spider, bee, and wasp venoms for agricultural purposes. We searched for patents registered worldwide using the keywords “animal species” AND “venom” associated with the Cooperative Patent Classification (CPC) subclasses, based on Google Patents by November 2020. The results indicate an increasing frequency in patents related to animal venoms. Scorpion, snake, and wasp appeared most frequently, besides other species. The inventors concentrate on two subclasses, namely new plant varieties development (A01H) and biopesticides (A01N). Monsanto and other giant agricultural and biotechnology companies lead the list in the number of patents. New varieties of crops, like soybean, corn, cotton, rice, and wheat, are the most frequent inventions. The benefits of using natural venoms in insect-resistant plant varieties and biopesticides are pertinent to agriculture, the environment, and human health.

The joint disease called pararamosis is an occupational disease caused by accidental contact with bristles of the caterpillar Premolis semirufa. The chronic inflammatory process narrows the joint space and causes alterations in bone structure and cartilage degeneration, leading to joint stiffness. Aiming to determine the bristle components that could be responsible for this peculiar envenomation, in this work we have examined the toxin composition of the caterpillar bristles extract and compared it with the differentially expressed genes (DEGs) in synovial biopsies of patients affected with rheumatoid arthritis (RA) and osteoarthritis (OA). Among the proteins identified, 129 presented an average of 63% homology with human proteins and shared important conserved domains. Among the human homologous proteins, we identified seven DEGs upregulated in synovial biopsies from RA or OA patients using meta-analysis. This approach allowed us to suggest possible toxins from the pararama bristles that could be responsible for starting the joint disease observed in pararamosis. Moreover, the study of pararamosis, in turn, may lead to the discovery of specific pharmacological targets related to the early stages of articular diseases. [ABSTRACT FROM AUTHOR]

Background: Elicitors and symptoms of anaphylaxis are age dependent. However, little is known about typical features of anaphylaxis in patients aged 65 years or more.Methods: The data from the Network for Online Registration of Anaphylaxis (NORA) considering patients aged ≥65 (elderly) in comparison to data from adults (18–64 years) regarding elicitors, symptoms, comorbidities, and treatment measures were analyzed.Results: We identified 1,123 elderly anaphylactic patients. Insect venoms were the most frequent elicitor in this group (p < 0.001), followed by drugs like analgesics and antibiotics. Food allergens elicited less frequently anaphylaxis (p < 0.001). Skin symptoms occurred less frequently in elderly patients (77%, p < 0.001). The clinical symptoms were more severe in the elderly (51% experiencing grade III/IV reactions), in particular when skin symptoms (p < 0.001) were absent. Most strikingly, a loss of consciousness (33%, p < 0.001) and preexisting cardiovascular comorbidity (59%, p < 0.001) were more prevalent in the elderly. Finally, adrenaline was used in 30% of the elderly (vs. 26% in the comparator group, p < 0.001) and hospitalization was more often required (60 vs. 50%, p < 0.001).Discussion and Conclusion: Anaphylaxis in the elderly is often caused by insect venoms and drugs. These patients suffer more often from cardiovascular symptoms, receive more frequently adrenaline and require more often hospitalization. The data indicate that anaphylaxis in the elderly tends to be more frequently life threatening and patients require intensified medical intervention. The data support the need to recognize anaphylaxis in this patient group, which is prone to be at a higher risk for a fatal outcome.

Copyright of Polish Journal of Allergology / Alergologia Polska is the property of Termedia Publishing House and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The level of fear of hymenoptera associated with stinging or envenomation may depend on situational factors and on trait anxiety characteristic of each patient. Aim: To assess the relationship between fear of stinging insects on the one hand and state anxiety and trait anxiety on the other in a group of patients with hymenoptera venom allergy. Material and methods: The study was conducted by the Department of Allergy, Clinical Immunology and Internal Diseases, Dr J. Biziel University Hospital No. 2 in Bydgoszcz, Poland. A total of 114 patients (71 women (63%) and 43 men (37%)) with hymenoptera venom allergy undergoing immunotherapy participated in the study. The State- Trait Anxiety Inventory (STAI) and a dedicated scale developed by the authors for this study were used. Results: State anxiety was found to significantly (p < 0.05) correlate with anxiety in the present moment (R = 0.247), in a situation of real danger (appearance of an insect) (R = 0.223) and during the spring and summer seasons (R = 0.278). Trait anxiety was found to significantly (p < 0.05) correlate with anxiety before immunotherapy (R = 0.261), in the present moment (R = 0.257), in a situation of real danger (appearance of an insect) (R = 0.254), and after an insect sting (R = 0.236). These were also weak correlations. The correlation between trait anxiety and anxiety during the spring and summer seasons was moderate (R = 0.331). Conclusions: The levels of trait and state anxiety are associated with the magnitude of the fear of the danger. Respondents showed a higher level of anxiety in a situation of danger and after an insect sting. [ABSTRACT FROM AUTHOR]

Introduction: Venom immunotherapy treatment (VIT) is the only causal treatment of hymenoptera venom anaphylaxis, which aims to provide long-lasting immunoprotection against severe reactions to subsequent stings. Aim: To reassess the compliance of VIT procedures in the Polish allergy centres with the European guidelines. Material and methods: A structured questionnaire survey conducted in all 33 VIT-centres. The response rate was 94%. Results: The ultrarush initial protocol was the most common protocol (71%, n = 22), usually lasting for 3.5 h (50%, n = 7). The most frequent (36%, n = 11) time interval from the initial to the first maintenance dose (MD) was 14 days, ranging from 7 to 35 days. All centres used an MD of 100 µg. The most frequent time interval between subsequent MDs was 4 weeks (58%, n = 18). Five years' of VIT was declared by 71% (n = 22). Before the termination of treatment, more than half of the centres (58%, n = 18) performed sIgE and almost half (42%, n = 13) performed skin tests. To confirm VIT efficacy, few centres (26%, n = 8) conducted the sting challenge. About half of centres provided the patients with an adrenalin auto-injector both at the time of initial diagnostics and at the end of treatment. More than half (55%, n = 17) used antihistamines in all patients. Almost half (45%, n = 14) declared to stop treatment with ß-blockers and almost one fourth (23%, n = 7) discontinued angiotensin-converting-enzyme inhibitors. Conclusions: In the most important procedures, there is a very high compliance with the guidelines. In the areas where the guidelines are not precise, we observed a large spread of results. [ABSTRACT FROM AUTHOR]

Introduction: Hymenoptera venom allergy (HVA) in some patients occurs with general symptoms involving respiratory and cardiovascular system with anaphylactic shock with constitutes a significant threat to life. Aim: Assessment of the prevalence of HVA in our own material. Material and methods: There were 498 patients after a general reaction to wasp and/or bee venom. The survey included questions: the type of stinging insect, body parts stung by insects, profession, frequency of stings by wasps and bees depending on professional activity, places of stings, clinical symptoms using the scale according to Muller, and the treatment following the sting. Among 498 patients, there were 281 women and 217 men. Results: Wasp stings were more frequent and affected 382 (77%) persons, while bee stings affected 116 (23%) persons. Limbs constituted the most common area of the body stung by both wasps and bees. The sting was more frequent in rural areas and during summer rest. A severe systemic reaction (class III and IV according to Muller) occurred more often in people stung by bees. The most common medications included intravenous glucocorticosteroids, calcium preparations and antihistamines. Intramuscular Adrenaline injection was used in 48% of patients, while only 15% received its prescription as an emergency medication. Bee stings were the most common cause of severe systemic symptoms. Conclusions: The treatment after the sting in a significant percentage of episodes still deviates from the recommendations of the guidelines, especially in the field of adrenaline recommendations for patients in case of a resting by an insect. [ABSTRACT FROM AUTHOR]

In an effort to improve surveillance capacity for the exotic red imported fire ant, Solenopsis invicta, a lateral flow immunoassay (LFA) was recently evaluated by Biosecurity Queensland staff in Australia. The purpose of the research was to assess the ability of the fire ant LFA to discriminate S. invicta from ants found in Australia and to conduct the first field evaluation of the test. In addition to S. invicta, 36 species of ants, collected mainly from Queensland, were evaluated by the LFA, including species from the Dolichoderinae (n = 7), Formicinae (n = 13), Myrmeciinae (n = 1), Myrmicinae (n = 11), Ponerinae (n = 3) and Pseudomyrmicinae (n = 1) subfamilies. The fire ant LFA test correctly identified S. invicta in every instance. No cross reactivity was observed in the other ant species. Field tests by staff previously unfamiliar with the test resulted in suggestions for improving ant collection and manipulation. The fire ant LFA appears to be suitable for use in Australia for rapid confirmation of potential new detections of S. invicta. [ABSTRACT FROM AUTHOR]

Lepidopterism refers to the adverse medical effects of contact with insects of the order Lepidoptera, which includes both moths and butterflies. These effects typically result from contact with an insect during the caterpillar (larval) stage. Lepidopterism involves multiple pathologic mechanisms, including direct toxicity of venom and mechanical irritant effects. Clinical patterns associated with contact with lepidoptera include localized stinging reactions, papular urticaria and dermatitis, urticarial wheals, and hemorrhagic diathesis. Accurate diagnosis of symptoms associated with contact with caterpillars, butterflies, or moths is nearly impossible without a reliable history of exposure, as the histology of exposure is nonspecific. Treatment is largely empiric and should be based on symptoms. We report a case of lepidopterism in a patient with acute cutaneous lesions following exposure to an adult-stage black butterfly (Hylesia nigricans). [ABSTRACT FROM AUTHOR]

llergen immunotherapy (AIT) with Hymenoptera venom (HV) shows high efficiency treating insect venom allergy, covering an almost 100-year-long history. Untreated patients with HV allergy can develop serious, potentially lethal sting reactions. Before starting AIT with HV, indication and contraindications, the presence of comorbidities and the intake of concomitant medications as well as individual risk factors have to be carefully evaluated. Application of HV-AIT entails an individually adapted procedure in case of undesired adverse events or initial failure to induce tolerance, as the final goal has to be the development of immunologic protection against anaphylactic sting reactions., Competing Interests: The author declares no conflict of interest., (© Dustri-Verlag Dr. K. Feistle.)

Abstract Insect venom phospholipases have been identified in nearly all clinically relevant social Hymenoptera, including bees, wasps and ants. Among other biological roles, during the envenoming process these enzymes cause the disruption of cellular membranes and induce hypersensitive reactions, including life threatening anaphylaxis. While phospholipase A2 (PLA2) is a predominant component of bee venoms, phospholipase A1 (PLA1) is highly abundant in wasps and ants. The pronounced prevalence of IgE-mediated reactivity to these allergens in sensitized patients emphasizes their important role as major elicitors of Hymenoptera venom allergy (HVA). PLA1 and -A2 represent valuable marker allergens for differentiation of genuine sensitizations to bee and/or wasp venoms from cross-reactivity. Moreover, in massive attacks, insect venom phospholipases often cause several pathologies that can lead to fatalities. This review summarizes the available data related to structure, model of enzymatic activity and pathophysiological roles during envenoming process of insect venom phospholipases A1 and -A2. Graphical abstract Image 1 Highlights • Phospholipases A1 (PLA1) and -A2 (PLA2) are prominent toxins in wasp/ant and bee venoms; respectively. • Insect venom PLA1 and PLA2 cause direct toxic effects and hypersensitive reactions including anaphylaxis. • After a massive attack, insect venom PLA1 and PLA2 activities often trigger several life-threatening pathologies. • Structural and functional characterization of PLA1 and PLA2 help to understand their role in the envenoming process. • Venom PLA1 and -A2 are marker allergens widely used in diagnosis of Hymenoptera venom allergy. [ABSTRACT FROM AUTHOR]

Background: Insect venom is the second most common cause of anaphylaxis outside of medical encounters. Stings cause over 20% of all anaphylactic deaths and 7% of anaphylaxis in children. To date, there have been no longitudinal studies of insect sting events or allergy in preschool children. Methods: A prospective longitudinal nested observational study in the BASELINE Birth Cohort Study (n = 2137). Sting‐related questions were asked at 6 and 12 months and 2 and 5 years. Skin prick testing (SPT) was performed at 2 and 5 years. SpIgE testing was performed on selected cases at 2 years. Results: Seventy‐seven children (6.8%) were stung by the age of 2. Of these, 25 (32.5%) reported adverse reactions (four systemic). Eleven (0.9%) had positive SPT at 2 years (eight bee, two wasp, one both). Four stung children had positive SPT. Two (one stung, one never stung) had positive spIgE to a venom component at 2 years. A total of 268 children (21.9%) were stung by 5 years, 144 (52.1%) reporting local reactions and none systemic. Four children (0.4%) had positive SPT at 5 years: one bee and three wasp. Of the 11 SPT‐positive children at 2 years, none were still positive at 5 years. Conclusion: This is the first longitudinal study of the natural history of hymenoptera stings and allergy in preschool children. Hymenoptera venom allergy is less common in this cohort than in adults. Systemic reactions were not medically documented in this population, in keeping with previous literature. This study confirms the poor correlation of IgE sensitization to venom with sting allergy and does not support the common parental request to screen children for sting allergy. [ABSTRACT FROM AUTHOR]

Summary: Background: CD16 was previously suggested to be a new marker of basophils that is subject to downregulation by FcεRI crosslinking. Certain compounds, including supraoptimal concentrations of the PKC inhibitors, bisindolylmaleimides, decouple the release of granules containing CD203c, CD63 and histamine, and may thus help to identify the mechanisms related to the CD16 externalization. Objective: We hypothesized that CD16 is differentially expressed on the surface of basophils in patients with birch pollen or insect venom allergy and is subject to a regulation in response to allergens. We also employed CD203c and CD63 externalization decoupling by bisindolylmaleimides. Methods: We performed a basophil activation test coupled with CD16 and histamine detection using cells isolated from patients with allergy to birch pollen or insect venom and negative controls. We employed two PKC inhibitors, bisindolylmaleimide II and Ro 31‐8220 at their supraoptimal concentrations and, after difficulties reproducing previously published data, we analyzed the fluorescence of these inhibitors alone. We identified the CD16 isoforms by sequencing nested RT‐PCR amplicons from flow cytometry sorted basophils and by cleaving the CD16b GPI anchor using a phospholipase C. Results: We provide the first evidence that CD16a is expressed as a surface antigen on a small subpopulation of human basophils in patients with respiratory and insect venom allergy, and this antigen shows increased surface expression following allergen challenge or FcεRI crosslinking. We rejected the apparent decoupling of the surface expression of basophil activation markers following the administration of bisindolylmaleimides. Conclusions & Clinical Relevance: The inclusion of αCD16 in negative selection cocktails selects against a subset of basophils that are CD16+ or CD16dim. Using CD16dim basophils and unstained leucocytes, we show that previous studies with supraoptimal concentrations of bisindolylmaleimides are likely flawed and are not associated with the differential expression of CD203c and CD63. [ABSTRACT FROM AUTHOR]

Although the importance of parasitoids as biocontrol agents has long been recognized, systematic studies of the physiological mechanisms are scarce, especially in those parasitoids that are able to successfully invade their hosts by activating host immune responses. This study explored this phenomenon by investigating the effects of ovarian fluid, venom and egg surface characteristics of Tetrastichus brontispae (Hymenoptera: Eulophidae) on host immunity. The results showed that the injection of venom alone induced higher phenoloxidase activity, while a mixture of ovarian plus venom fluids provoked higher granulocyte and plasmatocyte spreading ratios, highlighting the role that egg surface characteristics may play in successful parasitism. After thorough investigation, the presence of a hemomucin homologue was documented on the egg surface (which was named Tetrastichus brontispae adipocyte plasma membrane associated protein-like, TbAPMAP-like), while the absence of polydnaviruses, fibrous layers and virus-like filaments was confirmed. The higher encapsulation index of eggs incubated with TbAPMAP-like polyclonal antibody demonstrated the protection of the protein against encapsulation. These results contribute to our understanding of the mechanisms used by endoparasitoids to evade encapsulation during the early parasitism stage while enriching our knowledge of local active regulatory mechanisms. It is likely that this is the first study to determine the egg protective properties of TbAPMAP-like in host-parasite systems. [ABSTRACT FROM AUTHOR]

Vespa tropica , a social wasp locally found in Thailand is responsible for many out off the record accidental stings due to close encounters with human activities and because of the animal's highly potent venom. Phospholipase (PLA) is one of the major proteins commonly found in insect venom. In this work, V. tropica phospholipase was successfully isolated, purified and characterized. Three isoforms PLAs have been purified using reversed phase HPLC, and are named VesT1s (VesT1.01a, VesT1.01b and VesT1.02). They are not glycoproteins. VesT1.01s has a molecular weight of 33.72 kDa while for VesT1.02 a mass of 34 kDa was found. The deduced sequence of the mature VesT1.02 protein is composed of 301 amino acid residues (1005 bp), including the catalytic triad (Ser-His-Asp), which is similar to other wasp venom PLAs. The 12 cysteine residues found are conserved among venom PLA1. They form six disulfide bonds, and therefore have no free sulfhydryl groups. Based on homology modelling, VesT1.02 belongs to the α/β hydrolase fold family. Its structure is composed of 10 β-sheets and 11 α-helixes, characterized by a β-strand/εSer/α-helix structural motif, which contains the Gly-X-Ser-X-Gly consensus sequence. The shortened lid and shortened β9 loop, which play important roles in substrate selectivity, cause this enzyme to only exhibit PLA activity. Moreover, these PLAs have been shown to be highly thermally stable after heating at 100 °C for 5 min. We propose that an inserted Pro residue might be involved in this high thermo-stability. [ABSTRACT FROM AUTHOR]

Among venomous animals, Hymenoptera have been suggested as a rich source of natural toxins. Due to their broad ecological diversity, venom from Hymenoptera insects (bees, wasps and ants) have evolved differentially thus widening the types and biological functions of their components. To date, insect toxinology analysis have scarcely uncovered the complex composition of bee, wasp and ant venoms which include low molecular weight compounds, highly abundant peptides and proteins, including several allergens. In Hymenoptera, these complex mixtures of toxins represent a potent arsenal of biological weapons that are used for self-defense, to repel intruders and to capture prey. Consequently, Hymenoptera venom components have a broad range of pharmacological targets and have been extensively studied, as promising sources of new drugs and biopesticides. In addition, the identification and molecular characterization of Hymenoptera venom allergens have allowed for the rational design of component-resolved diagnosis of allergy, finally improving the outcome of venom immunotherapy (VIT). Until recently, a limited number of Hymenoptera venoms had been unveiled due to the technical limitations of the approaches used to date. Nevertheless, the application of novel techniques with high dynamic range has significantly increased the number of identified peptidic and proteinaceous toxins. Considering this, the present review summarizes the current knowledge about the most representative Hymenoptera venom peptides and proteins which are under study for a better understanding of the insect-caused envenoming process and the development of new drugs and biopesticides. [ABSTRACT FROM AUTHOR]

Introduction: The Megalopyge opercularis caterpillar is covered with spines that break off and release venom on contact, resulting in severe pain, erythema, rash, and other adverse effects. In Texas, these caterpillars are abundant and of potential health threat. This study describes M opercularis caterpillar stings reported to Texas poison centers.Methods: Cases were M opercularis caterpillar stings reported to Texas poison centers during 2000-2016. The distribution of stings was determined related to exposure circumstances and management.Results: There were 3484 M opercularis caterpillar stings reported during 2000-2016. The annual number of stings did not consistently change over the 17-year time period. The monthly number of stings was highest in July (12%) and October to November (59%). The patients were female in 53% of cases and aged 20 years or more in 56%. The sting occurred at the patient's own residence in 91% of cases. The patients were managed outside of a healthcare facility in 89% of cases; 93% of the patients were known or expected to have no or at most minor clinical effects. Dermal clinical effects were reported in 90% of cases, the most common being irritation/pain (84%), puncture/wound (45%), erythema/flushed (29%), and edema (15%).Conclusions: M opercularis caterpillar stings reported to Texas poison centers were more frequently reported in July and October to November. Most of the patients were adults. The majority of patients were managed outside of healthcare facilities and did not have serious outcomes. Most of the adverse clinical effects were dermal in nature. [ABSTRACT FROM AUTHOR]

Background: Insect venom allergy is common and greatly impairs patients’ quality of life. Additionally, low compliance with carrying emergency medication is reported. The aim of our study was to analyze the disease burden, levels of anxiety and depression, and to evaluate attitudes towards the set of emergency medication in affected patients. Methods: Between April 2016 and January 2017, patients ≥18 years visiting our department because of an insect venom allergy were asked to complete a paper-based questionnaire. The questionnaire assessed willingness to pay (WTP), the Hospital Anxiety and Depression Scale (HADS), subjective anxiety levels, willingness to carry the set of emergency medication, self-assurance in using it, compliance with carrying it, and reasons for not always carrying it. Results: 55 patients (81.8% wasp allergy) were included. On average, WTP for a complete cure was EUR 1,727 (median: 500). Using the HADS, 14.5% showed definite anxiety disorders while 5.5% had significant depression disorders. Most patients stated to carry the emergency medication “always” (25.5%) or “almost always” (47.3%). “Forgetfulness” (36.4%) was reported as the main reason for not always carrying the medication, followed by “too big” (18.2%). Conclusions: In our patient cohort, insect venom allergy was associated with a moderate disease burden and a good compliance with carrying the emergency medication. However, several of our participants demonstrated borderline or significant anxiety and/or depression disorders. In this regard, this study highlights the necessity to regularly ask the patient about the psychological well-being to identify patients needing psychological support. [ABSTRACT FROM AUTHOR]

Spider venoms are complex mixtures composed of a variety of compounds, including salts, small organic molecules, peptides, and proteins. But, the venom of a few species is dangerous to humans. High levels of chemical diversity make spider venoms attractive subjects for chemical prospecting. Many spider venom components show potential activity against a wide range of human diseases. However, the development of novel venom-derived therapeutics requires an understanding of their mechanisms of action. This review will highlight the structures, activities and the possible mechanisms of action of spider venoms and their components against cancer, microbial infections, and pain. [ABSTRACT FROM AUTHOR]

Abstract: The females of the spider wasps (Hymenoptera: Pompilidae) hunt spiders to provision their larvae. The genital structures of pompilid females are modified in a sting that is used for paralyzing the prey (spiders) and defense. The skeleto‐muscular structure of the sting apparatus of a typical representative of the family (Cryptocheilus versicolor) is examined. The shape of sclerites, their relative positions and articulations are described. Some morphological adaptations are described for the first time. The wide anal arc of the tergum IX provides a stiff support for the muscles that move the valvulae. The resilin structures in the areas of articulation support the work of muscles and in some cases replace them. The 1st valvulae form a venom duct along their entire length, which provides the delivery of the venom to a specific point. An unpaired flap in the venom duct provides a dose of venom in the sting. This mechanism probably enhances the speed and accuracy of the wasp's sting movements. Functions of muscles and interactions of the structures of the sting apparatus of C. versicolor are discussed. [ABSTRACT FROM AUTHOR]

The term allergic angina, introduced for the first time by Nicholas Kounis in 1991, initially referred to the coexistence of acute coronary syndromes with allergy or hypersensitivity. At present, it is believed that Kounis syndrome is a particular case of systemic disease, with multiorgan arterial involvement generated during immediate hypersensitivity reactions. Myocardial bridging (MB), a condition that can induce coronary artery spasm, has long been regarded as a benign condition. Since both pathologies are associated with arterial spasm, Kounis syndrome and MB are considered to be confounding pathologies for acute coronary syndromes, and their association is quite a rare finding. To date, there are no precise data on the epidemiology, and the population affected by Kounis syndrome seems to be highly heterogeneous. Since this is a rare disease, even less is known about possible different phenotypes, including MB overlap. We report a case of type I variant Kounis syndrome associated with MB with no evidence of coronary artery disease, occurring as late presentation, following a severe systemic reaction (anaphylaxis) induced by a Hymenoptera sting. At present, only two other cases of type I and one case of type II Kounis syndrome occurring in patients with myocardial bridging have been described.

The sensitivity of vertebrate citrated plasma to pro- and anticoagulant venom or toxins occurs on a microscale level (micrograms). Although it improves responses to agonists, recalcification triggers a relatively fast thrombin formation process in mammalian plasma. As it has a natural factor XII deficiency, the recalcification time (RT) of chicken plasma (CP) is comparatively long [≥ 1800 seconds (s)]. Our objective was to compare the ability of bee venom phospholipase A2 (bvPLA2) to neutralize clot formation induced by an activator of coagulation (the aPTT clot) in recalcified human and chicken plasmas, through rotational thromboelastometry. The strategy used in this study was to find doses of bvPLA2 that were sufficient enough to prolong the clotting time (CT) of these activated plasmas to values within their normal RT range. The CT of CP was prolonged in a dose-dependent manner by bvPLA2, with 17 ± 2.8 ng (n = 6) being sufficient to displace the CT values of the activated samples to ≥ 1800 s. Only amounts up to 380 ± 41 ng (n = 6) of bvPLA2 induced the same effect in activated human plasma samples. In conclusion, the high sensitivity of CP to agonists and rotational thromboelastometry could be useful. For example, during screening procedures for assaying the effects of toxins in several stages of the coagulation pathway, such as clot initiation, formation, stability, strength, or dissolution.

Assassin bugs (Reduviidae) produce venoms that are insecticidal, and which induce pain in predators, but the composition and function of their individual venom components is poorly understood. We report findings on the venom system of the red-spotted assassin bug Platymeris rhadamanthus, a large species of African origin that is unique in propelling venom as a projectile weapon when threatened. We performed RNA sequencing experiments on venom glands (separate transcriptomes of the posterior main gland, PMG, and the anterior main gland, AMG), and proteomic experiments on venom that was either defensively propelled or collected from the proboscis in response to electrostimulation. We resolved a venom proteome comprising 166 polypeptides. Both defensively propelled venom and most venom samples collected in response to electrostimulation show a protein profile similar to the predicted secretory products of the PMG, with a smaller contribution from the AMG. Pooled venom samples induce calcium influx via membrane lysis when applied to mammalian neuronal cells, consistent with their ability to cause pain when propelled into the eyes or mucus membranes of potential predators. The same venom induces rapid paralysis and death when injected into fruit flies. These data suggest that the cytolytic, insecticidal venom used by reduviids to capture prey is also a highly effective defensive weapon when propelled at predators.

Venoms of social wasps have in their composition proteins, peptides, among others and several of these compounds were evaluated for their function in the venom, however, there is still no study of the quantification of free amino acids of venom of social wasps. The peptides and proteins of the venom can originate in the medium amino acids or other molecules by the rupture of the peptide bonds. Therefore, the objective was evaluated the composition of the free amino acid in venom of the social wasp Polistes lanio and validated a method for free amino acids analysis using different forms of preservation of this venom. For this, the venom of P. lanio was analyzed direct and partitioned (liquid-liquid with organic solvents) by High Performance Liquid Chromatography. For validation of the amino acids, parameters as linearity, stability and recovery of the assay method were evaluated by the analyzing it fresh or frozen, and before or after extraction with organic solvents. The free amino acids were recovered from these samples at rates ranging from 93.2- 99.0%. The data obtained indicate that the freezing, storage and extraction with organic solvents does not lead to an increase in the amino acids content of proteins and peptides. [ABSTRACT FROM AUTHOR]

Résumé Les données épidémiologiques concernant la mortalité par anaphylaxie sont rares et discordantes. Notre objectif était de déterminer le taux de mortalité par anaphylaxie (exprimé par million et par an) en France métropolitaine et d’analyser l’évolution entre 1979 et 2011, les spécificités selon la cause (iatrogène, venin d’insectes, aliment ou non spécifiée), le sexe et l’origine géographique. Méthodes Les données ont été obtenues : (1) du CépiDC (Inserm) pour colliger les cas de décès par anaphylaxie et les données complémentaires (sexe, âge, origine géographique lors du décès) ; (2) de l’INSEE pour déterminer les populations de référence. Un modèle de régression logistique multivariée a été utilisé pour évaluer l’impact de l’âge, du sexe, de l’origine géographique lors du décès, de la durée sur les décès par anaphylaxie. Résultats Au total, 1603 décès ont été analysés : 1564 chez l’adulte et 39 chez l’enfant (âge < 19 ans). La prévalence globale des décès par anaphylaxie était de 0,84 par million et par an (IC 95 % : 0,80–0,88), comprise entre 0,08 (IC 95 % : 0,05–0,10) chez l’enfant et 1,12 (IC 95 % : 1,06–1,17) chez l’adulte. Pendant la période, il existait une diminution de ce taux de 2,1 % dans la population générale (IC 95 % : −2,6 à −1,7 ; p < 10 −4 ) et de 2,5 % (IC 95 % : −5,6–0,9) dans la population pédiatrique. Le taux de mortalité était plus élevé chez les hommes (1,08 [IC 95 % : 1,00–1,16] que chez les femmes (0,86 [IC 95 % : 0,80–0,92]) ( p < 10 −4 ). Les causes de décès par anaphylaxie étaient iatrogènes (63 %), principalement liés aux médicaments, les venins d’insectes (14 %) et les aliments (0,6 %). Dans 23 % des cas, la cause n’était pas spécifiée. Le taux de mortalité était le plus élevé chez les personnes âgées de plus de 70 ans (3,50 [IC 95 % : 3,25–3,76]). Le taux de mortalité par décès liés aux venins d’insectes était plus élevé dans le sud de la France (0,16 [IC 95 % : 0,13–0,19]) que dans le nord (0,11 [IC 95 % : 0,09–0,13]) ( p = 0,004). Seulement 8 décès (dont 7 survenus chez des personnes âgées de moins de 32 ans) par anaphylaxie de cause alimentaire étaient identifiés. L’analyse multivariée a montré que l’âge, l’évolution dans le temps et le sexe masculin étaient des facteurs de risque de décès par anaphylaxie toute cause confondue ( p < 10 −4 ). Conclusion La mortalité par anaphylaxie diminue de 2 % par an au cours des 3 dernières décennies en France métropolitaine. Les causes iatrogéniques sont les principales causes. L’âge et le sexe masculin sont des facteurs de risque d’anaphylaxie létale, en dehors des anaphylaxies de cause alimentaire. Data about anaphylaxis mortality are limited and conflicting. Objective To determine the anaphylaxis mortality rate (AMR), time trends and specificities according to trigger factor, age group, sex and geographical region in France from 1979 to 2011. Patients and methods Data were obtained from databases of: (1) the French Mortality Center (CepiDC) to collect cases of lethal anaphylaxis and; (2) the French Statistics Institute (INSEE) to define the reference populations. AMRs were expressed per million persons/year. Results Overall, 1603 cases of deaths from anaphylaxis were collected: 1564 in adults and 39 in children (age < 19 years). Overall and pediatric AMRs were respectively 0.83 (95%CI, 0.80–0.88) and 0.08 (95%CI: 0.05–0.10). AMR was higher in men (1.08 [95%CI, 1.00–1.16] than women (0.86 [95%CI, 0.80–0.92]) ( P < 10 −4 ). Annual percentage change for the case fatality rate was −2.1% (95%CI, −2.6; −1.7) indicating a decrease during the study period ( P < 10 −4 ). Causes of anaphylactic shock were iatrogenic (63%), mostly drugs, venom (14%) and food (0.6%). AMR was the highest in persons aged ≥ 70 years (3.50 [95%IC: 3.25–3.76]). The venom-induced mortality rate was higher in the south of France (0.16) compared to the north (0.11) ( P = 0.003). Only eight food-induced fatalities were recorded (age < 32 years in seven). Multivariate analysis showed that greater age, changes over time, and male gender were associated with a significant risk for death from anaphylaxis, irrespective of cause ( P < 10 −4 ). Conclusion Overall, AMR has decreased over the last three decades in France (2%/year). Iatrogenic causes are the most frequently involved trigger. Higher age and male gender are risk factors for fatal anaphylaxis of any cause other than food-related causes. [ABSTRACT FROM AUTHOR]

Quantitative structure–activity relationship models for bee toxicity have been built up using CORAL software (http://www.insilico.eu/coral). The approach is based on the Monte Carlo technique. The molecular structure for the quantitative structure–activity relationship analysis has been presented by the simplified molecular input-line entry system. The so-called balance of correlations and the traditional scheme of building up quantitative structure–activity relationship models are compared in this work. The traditional scheme is based on three basic sets of compounds: training, calibration, and validation, whereas, the balance of correlations is based on four sets: active training, invisible training, calibration, and validation. As rule, the balance of correlations gives better models in comparison with the traditional scheme. The statistical characteristics of the models are quite good. Possible mechanistic interpretations and indications for the domain of applicability of these models are suggested. [ABSTRACT FROM PUBLISHER]

Aspartylglucosaminidase (AGA) is a low-abundance intracellular enzyme that plays a key role in the last stage of glycoproteins degradation, and whose deficiency leads to human aspartylglucosaminuria, a lysosomal storage disease. Surprisingly, high amounts of AGA-like proteins are secreted in the venom of two phylogenetically distant hymenopteran parasitoid wasp species, Asobara tabida (Braconidae) and Leptopilina heterotoma (Cynipidae). These venom AGAs have a similar domain organization as mammalian AGAs. They share with them key residues for autocatalysis and activity, and the mature α- and β-subunits also form an (αβ)2 structure in solution. Interestingly, only one of these AGAs subunits (α for AtAGA and β for LhAGA) is glycosylated instead of the two subunits for lysosomal human AGA (hAGA), and these glycosylations are partially resistant to PGNase F treatment. The two venom AGAs are secreted as fully activated enzymes, they have a similar aspartylglucosaminidase activity and are both also efficient asparaginases. Once AGAs are injected into the larvae of the Drosophila melanogaster host, the asparaginase activity may play a role in modulating their physiology. Altogether, our data provide new elements for a better understanding of the secretion and the role of venom AGAs as virulence factors in the parasitoid wasps’ success. [ABSTRACT FROM AUTHOR]

Contact with the caterpillars of the pine processionary moth (CPPM) Thaumetopoea pityocampa induces severe local allergic reactions. The purpose of this large-scale retrospective cohort-study was to describe the clinical manifestations and related risk factors of CPPM exposure. This cohort-study included 109 dogs between the years of 2000 and 2016. Tongue lesions ranging from oedema to severe necrosis were observed in 94/109 dogs (86%). The following systemic signs were observed in 60/109 dogs (55%): vomiting (52/109, 48%), dyspnoea (6/109, 5%), hypovolemia (4/109, 4%) and diarrhoea (2/109, 2%). Based on the time elapsed from CPPM contact to the first oral flushing, three groups were defined: <2 h (group 1, 37/105, 35%), 2 h–6 h (group 2, 39/105, 37%) and >6 h (group 3, 29/105, 28%). Tongue necrosis (TN) at admission was significantly more common in the dogs in group 3 than those in groups 1 and 2 (45% vs. 5% and 5% respectively, p = 0.0002). In addition, the development of TN during hospitalisation was significantly more common in the dogs in group 3 (65%) than in those in the other groups (21% in group 1, p = 0.02) and 31% in group 2, p = 0.001). The dogs in group 3 presented a 14.63-fold higher risk of TN at admission and a 3.78-fold higher risk of developing necrosis during hospitalisation compared with the other groups. The survival rate after exposure was 97%. Long-term follow-up data were available for 69/109 dogs (63%). Twenty-three dogs (37%) had persistent, definitive TN without major consequences on quality of life. Elapsed time between contact and first oral flushing appears to be a key determinant for the progression of necrotic lesions, and the best results were observed when flushing occurred within 6 h of contact. The prognosis of CPPM envenomation is excellent, with a short hospitalisation duration. [ABSTRACT FROM AUTHOR]

The effect of Habrobracon hebetor venom and the role of the adipokinetic hormone (AKH) in poisoned adult females of the firebug Pyrrhocoris apterus were studied 24 and 48 h after treatments. Venom application elicited total neuromuscular paralysis in firebugs, but the co-application of venom and Pyrap-AKH significantly reduced paralysis (up to 3.2 times) compared to the application of venom only. Although the mechanisms of their action are unknown, both agents might affect neuromuscular junctions. Venom application significantly increased the expression of both P. apterus Akh genes ( Pyrap - Akh 5.4 times and Peram - Cah - II 3.6 times), as well as the level of AKHs in the central nervous system (2.5 times) and haemolymph (3.0 times). In the haemolymph, increased AKH levels might have led to the mobilization of stored lipids, which increased 1.9 times, while the level of free carbohydrates remained unchanged. Total metabolism, monitored by carbon dioxide production, significantly declined in paralysed P. apterus individuals (1.4 times and 1.9 times, 24 and 48 h after the treatment, respectively), probably because of a malfunction of the muscular system. The results suggest an active role of AKH in the defence mechanism against the stress elicited by neuromuscular paralysis, and the possible involvement of this hormone in neuronal/neuromuscular signalling. [ABSTRACT FROM AUTHOR]

Currently, new antimicrobial molecules extracted or obtained by natural sources, could be a valide alternative to traditional antibiotics. Most of these molecules are represented by antimicrobial peptides (AMPs), which are essential compounds of insect, arachnids and centipedes venom. AMPs, due to their strong effectiveness, low resistance rates and peculiar mode of action, seem to have all the suitable features to be a powerful weapon against several bacteria, especially considering the increasing antibiotic-resistance phenomena. The present literature review focuses on the antibacterial activity of bee, wasp, ant, scorpion, spider and scolopendra crude venom and of their main biological active compounds. After a brief overview of each animal and venom use in folkloristic medicine, this review reports, in a comprehensive table, the results obtained by the most relevant and recent researches carried out on the antibacterial activity of different venom and their AMPs. For each considered study, the table summarizes data concerning minimal inhibitory concentration values, minimal bactericidal concentration values, the methods employed, scientific name and common names and provenience of animal species from which the crude venom and its respective compounds were obtained. [ABSTRACT FROM AUTHOR]

Many species of endoparasitoid wasps provide biological control services in agroecosystems. Although there is a great deal of information on the ecology and physiology of host/parasitoid interactions, relatively little is known about the protein composition of venom and how specific venom proteins influence physiological systems within host insects. This is a crucial gap in our knowledge because venom proteins act in modulating host physiology in ways that favor parasitoid development. Here, we identified 37 possible venom proteins from the polydnavirus-carrying endoparasitoid Cotesia chilonis by combining transcriptomic and proteomic analyses. The most abundant proteins were hydrolases, such as proteases, peptidases, esterases, glycosyl hydrolase, and endonucleases. Some components are classical parasitoid venom proteins with known functions, including extracellular superoxide dismutase 3, serine protease inhibitor and calreticulin. The venom contains novel proteins, not recorded from any other parasitoid species, including tolloid-like proteins, chitooligosaccharidolytic β-N-acetylglucosaminidase, FK506-binding protein 14, corticotropin-releasing factor-binding protein and vascular endothelial growth factor receptor 2. These new data generate hypotheses and provide a platform for functional analysis of venom components. [ABSTRACT FROM AUTHOR]

Background The European Academy of Allergy and Clinical Immunology ( EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy ( AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost-effectiveness and safety of AIT in the management of insect venom allergy. Methods We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta-analysed. Results Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy ( VIT) could substantially reduce the risk of subsequent severe systemic sting reactions ( OR = 0.08, 95% CI 0.03-0.26); meta-analysis showed that it also improved disease-specific quality of life (risk difference = 1.41, 95% CI 1.04-1.79). Adverse effects were experienced in both the build-up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost-effectiveness suggested that VIT was likely to be cost-effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. Conclusions The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease-specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost-effectiveness of VIT needs to be established. [ABSTRACT FROM AUTHOR]

[Display omitted] Limacodidae is a family of lepidopteran insects comprising >1500 species. More than half of these species produce pain-inducing defensive venoms in the larval stage, but little is known about their venom toxins. Recently, we characterised proteinaceous toxins from the Australian limacodid caterpillar Doratifera vulnerans , but it is unknown if the venom of this species is typical of other Limacodidae. Here, we use single animal transcriptomics and venom proteomics to investigate the venom of an iconic limacodid, the North American saddleback caterpillar Acharia stimulea. We identified 65 venom polypeptides, grouped into 31 different families. Neurohormones, knottins, and homologues of the immune signaller Diedel make up the majority of A. stimulea venom, indicating strong similarities to D. vulnerans venom, despite the large geographic separation of these caterpillars. One notable difference is the presence of RF-amide peptide toxins in A. stimulea venom. Synthetic versions of one of these RF-amide toxins potently activated the human neuropeptide FF1 receptor, displayed insecticidal activity when injected into Drosophila melanogaster , and moderately inhibited larval development of the parasitic nematode Haemonchus contortus. This study provides insights into the evolution and activity of venom toxins in Limacodidae, and provides a platform for future structure-function characterisation of A. stimulea peptide toxins. [ABSTRACT FROM AUTHOR]

Abstract Viruses exhibit rapid mutational capacity to trick and infect host cells, sometimes assisted through virus-coded peptides that counteract host cellular immune defense. Although a large number of compounds have been identified as inhibiting various viral infections and disease progression, it is urgent to achieve the discovery of more effective agents. Furthermore, proportionally to the great variety of diseases caused by viruses, very few viral vaccines are available, and not all are efficient. Thus, new antiviral substances obtained from natural products have been prospected, including those derived from venomous animals. Venoms are complex mixtures of hundreds of molecules, mostly peptides, that present a large array of biological activities and evolved to putatively target the biochemical machinery of different pathogens or host cellular structures. In addition, non-venomous compounds, such as some body fluids of invertebrate organisms, exhibit antiviral activity. This review provides a panorama of peptides described from animal venoms that present antiviral activity, thereby reinforcing them as important tools for the development of new therapeutic drugs.

Assassin flies (Diptera: Asilidae) inject paralysing venom into insect prey during hunting, but their venoms are poorly characterised in comparison to those produced by spiders, scorpions, or hymenopteran insects. Here we investigated the composition of the venom of the giant Australian assassin fly Dolopus genitalis using a combination of insect microinjection assays, calcium imaging assays of mammalian sensory neurons, proteomics and transcriptomics. Injection of venom into blowflies (Lucilia cuprina) produced rapid contractile paralysis (PD50 at 1 min = 3.1 μg per fly) followed by death, and also caused immediate activation of mouse dorsal root ganglion neurons (at 50 ng/μL). These results are consistent with venom use for both prey capture and predator deterrence. Paragon searches of tandem mass spectra of venom against a translated thoracic gland RNA-Seq database identified 122 polypeptides present in the venom, including six linear and 21 disulfide-rich peptides. Some of these disulfide-rich peptides display sequence homology to peptide families independently recruited into other animal venoms, including inhibitor cystine knots, cystine-stabilised α/β defensins, Kazal peptides, and von Willebrand factors. Numerous enzymes are present in the venom, including 35 proteases of the S1 family, proteases of the S10, C1A, M12A, M14, and M17 families, and phosphatase, amylase, hydrolase, nuclease, and dehydrogenase-like proteins. These results highlight convergent molecular evolution between the assassin flies and other venomous animals, as well as the unique and rich molecular composition of assassin fly venom.

Diagnostic testing of patients who present for evaluation of insect venom allergy can involve many levels of investigation. A detailed initial history is critical for diagnosis and prognosis. The severity of previous sting reactions and the presence or absence of urticaria or hypotension predict severe future sting reactions and underlying mast cell disorders. Venom skin tests and specific IgE measurement can confirm the diagnosis but have limited positive predictive value for the frequency and severity of future sting reactions. Testing for serum IgE to recombinant venom component allergens can distinguish true allergy from cross-reactivity to honey bee and yellowjacket venoms. Basophil activation tests can improve the detection of venom allergy and predict the severity of reactions and the efficacy of venom immunotherapy but are limited in availability. An elevated basal serum tryptase level is an important marker for severe sting anaphylaxis and underlying mast cell disorders (eg, hereditary α-tryptasemia and clonal mast cell disease). When there is high suspicion (eg, using the Red Espanola de Mastocytosis score), bone marrow biopsy is the definitive tool to characterize mast cell disorders that are associated with the most severe outcomes in patients with insect sting allergy., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)