Insect Venom Research Articles

Adverse events associated with venomous insect immunotherapy and clinical outcomes in 82 dogs (2002–2020)

Limited information is known on adverse events and efficacy associated with venomous insect immunotherapy (VIT) in canine patients. To assess adverse events associated with VIT and perceived efficacy of VIT. Records from 82 client-owned animals which received VIT were assessed. A retrospective review of records from 2002 to 2020. Clinical history, adverse events during therapy and observations following field stings were collected from all records. Patients were grouped intoreactors and nonreactors based on whether or not an adverse event had occurred during therapy. Records were evaluated to determine if a field sting had occurred and the severity of the reaction was compared to pretreatment reaction. Of 82 patients that were identified, 26 experienced a minimum of one adverse event. No deaths or severe anaphylactic reactions were reported. The most common adverse event was gastrointestinal upset. The overall reaction rate per injection was 2.8%. Only variation in sensitisation level (the minimum concentration of venom which elicited a positive intradermal reaction) was significantly different between groups (P = 0.014). Forty-one field challenges in 26 patients were documented. Therapy reduced the severity of reactions in 87.8% of challenges. No deaths were reported. Venom immunotherapy appears to be a safe and efficacious treatment for prevention of anaphylaxis due to insect stings in canine patients.

28517 Increasing prevalence of insect venom allergy among adolescents

Introduction: Hymenoptera insects can cause immediate hypersensitivity reactions that range from a mild, local reaction, to systemic sting reactions which may cause fatalities. The purpose of this study was to identify trends and associated risk factors in prevalence rates of insect sting allergy among adolescents in Israel.

A hidden deadly venomous insect: First eco-epidemiological assessment and risk mapping of lonomism in Argentina.

BackgroundEnvenomation by the South American Lonomia saturniid caterpillars, named lonomism, constitutes an emerging and somewhat neglected public health issue in Argentina and neighboring countries. Considering that there is an intricate relationship between environment and human health in such cases, this study aimed to analyze the eco-epidemiological profile of 40 accidents and 33 occurrences of Lonomia spp. in Misiones (Argentina) between January 2014 and May 2020.Methodology/Principal findingsWe described the eco-epidemiological variables and characterized the abiotic scenario of such cases. Additionally, we obtained a density map that shows the punctual intensity of Lonomia records throughout Misiones. Most of the accidents occurred in the Department of Guaraní and involved male victims younger than 20 years old. The accidental/occasional occurrence of Lonomia spp. (considering both adult and caterpillar stages together) was significantly higher in the rural area, whereas only adult specimens were found in urban areas. We determined that the presence of this insect in Misiones is positively related to higher temperatures and solar radiation, and larger precipitation and evapotranspiration throughout the year.Conclusion/SignificanceThis study represents an initial step towards the global understanding of lonomism as a public health problem in Argentina. It provides a map of the risk level for this envenomation in Misiones, which could help authorities address public health policy efforts to implement sustainable strategies for prevention and response to this threat in Northeastern Argentina and neighboring regions.

Expression of MRGPRX2 in skin mast cells of patients with maculopapular cutaneous mastocytosis

MRGPRX2 is a G protein–coupled receptor that is predominantly expressed in human skin mast cells (MCs).1,2 It is activated by a wide spectrum of cationic ligands including host defense antimicrobial peptides, neuropeptides, Hymenoptera venom, neuromuscular-blocking drugs, and the fluoroquinolone family of antibiotics.3 Systemic mastocytosis (SM) is characterized by the abnormal accumulation of MCs in different organs of the body and may occur with or without cutaneous disease.4 Giavina-Bianchi et al5 recently reported a case of a patient with SM who developed 5 episodes of anaphylaxis in response to insect venom and ciprofloxacin used to treat urinary tract infection.

Basophil Activation Test for Allergy Diagnosis.

The basophil activation test (BAT) is a complementary in vitro diagnostic test that can be used in addition to clinical history, skin test (ST), and specific IgE (sIgE) determination in the evaluation of IgE-mediated allergic reactions to food, insect venom, drugs, as well as some forms of chronic urticaria. However, the role of this technique in the diagnostic algorithms is highly variable and not well determined. BAT is based on the determination of basophil response to allergen/drug cross-linking IgE activation through the measurement of activation markers (such as CD63, CD203c) by flow cytometry. This test can be a useful and complementary tool to avoid controlled challenge teststo confirm allergy diagnosis, especially in subjects experiencing severe life-threatening reactions. In general, the performance of BAT should be considered if i) the allergen/drug produces false positive results in ST; ii) there is no allergen/drug source to use for ST or sIgE determination; iii) there is discordance between patient history and ST or sIgE determination; iv) symptoms suggest that ST may result in systemic response; v) before considering a CCT to confirm the culprit allergen/drug. The main limitations of the test are related to non-optimal sensitivity, especially in drug allergy, the need to perform the test no longer than 24 h after sample extraction, and the lack of standardization between laboratories in terms of procedures, concentrations, and cell markers.

Emergency medicine updates: Anaphylaxis.

Anaphylaxis is a potentially deadly condition that requires emergent therapy. While frequently treated in the emergency department (ED), recent evidence updates may improve the diagnosis and management of this condition. This paper evaluates key evidence-based updates concerning the diagnosis and management of anaphylaxis for the emergency clinician. The presentation of anaphylaxis can vary. Current diagnostic criteria can be helpful when evaluating patients for anaphylaxis, though multiple criteria exist. While the most common causes of anaphylaxis include medications, insect venom, and foods, recent literature has identified an IgE antibody response to mammalian galactose alpha-1,3-galactose, known as alpha-gal anaphylaxis. Epinephrine is the first-line therapy and is given in doses of 0.01 mg/kg (up to 0.5 mg in adults) intramuscularly (IM) in the anterolateral thigh. Intravenous (IV) epinephrine administration is recommended in patients refractory to IM epinephrine and IV fluids, or those with cardiovascular collapse. Antihistamines and glucocorticoids should not delay administration of epinephrine and do not demonstrate a significant reduction in risk of biphasic reactions. Biphasic reactions may affect 1-7% of patients with anaphylaxis. Risk factors for biphasic reaction include severe initial presentation and repeated doses of epinephrine. Disposition of patients with anaphylaxis requires consideration of several factors. Emergency clinicians must be aware of current updates in the evaluation and management of this disease.

COVID-19-Impfungen von allergischen Patienten im zeitlichen Zusammenhang mit einer Allergen-Immuntherapie (AIT) – Ein Positionspapier des Ärzteverbandes Deutscher Allergologen (AeDA) und der Deutschen Gesellschaft für Allergologie und Klin

Background: Vaccinations against Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are intended to induce an immune response in the sense of protection against infection/disease. Allergen-specific immunotherapy (AIT) is also thought to induce a (different) immune response in the sense of tolerance to allergens. There is uncertainty among patients and physicians regarding the use of vaccination and AIT in temporal relation, which this position paper aims to clarify. The four vaccines currently approved in Germany for vaccination against SARS-CoV-2 are described and possible immunological interactions with AIT are highlighted, as well as practical recommendations for action. Methods: Based on the current internationally published literature, this position paper provides specific recommendations for action regarding the use of AIT in temporal relation to a SARS-CoV-2 vaccination. Results: The present recommendations for action relate to the following conditions for which AIT is used i) allergic rhinitis, ii) allergic bronchial asthma, iii) insect venom allergy, iiii) food allergy (peanut). Conclusions: If vaccination is imminent, initiation of subcutaneous (SCIT), sublingual (SLIT), or oral (OIT) AIT should be delayed until 1 week after the 2nd vaccination date. Thus, there should generally be an interval of approximately 1 week between SCIT and COVID-19 vaccination. For the continuation of an ongoing AIT, we recommend an interval of 1 week before and after vaccination for SCIT. For SLIT and OIT, we recommend taking them up to the day before vaccination and taking a break from SLIT and OIT for 2 – 7 days after vaccination.

Insect Venom Toxin Peptides, its Antimicrobial Effects and Host Immune Responses: A Review

Insect Venom Toxin Peptides, its Antimicrobial Effects and Host Immune Responses: A Review

1-Boc-Piperidine-4-Carboxaldehyde Prevents Binge-Eating Behaviour and Anxiety in Rats

Background: Piperidines are biogenic amines studied mainly in toxicology because they were initially found as alkaloids from peppers and insect venoms. Piperidines are also produced in the human body, and their actions seem to be related to wakefulness/sleep and other cognitive phenomena. Piperidines have been minimally characterized for therapeutic applications. In this context, 1-Boc-piperidine-4-carboxaldehyde (1-Boc-piperidine) is a piperidine-derivative molecule with no mechanism of action reported, although its uses include the synthesis of GPR119 selective agonists that have been patented as anti-obesity drugs. Objectives: The aim of this work was to study the effects of 1-Boc-piperidine on binge-eating behaviour and anxiety in Wistar rats. Methods: In experimental protocol 1, binge-eating behaviour was induced in animals that received pre-treatment (i.p.) with (i) vehicle (methanol 10%; 1 mL/kg), (ii) 1-Boc-piperidine (1 µmol kg⁻¹), or (iii) 1-Boc-piperidine (10 µmol kg⁻¹). In experimental protocol 2, mildly stressed animals were evaluated in the elevated plus maze under the acute effects of the pre-treatments applied in experimental protocol 1. Results and Conclusions: 1-Boc-piperidine decreased, in a dose-dependent manner, the intake of calories from a succulent hyper-caloric food in a binge-eating protocol in female rats, whereas the acute exposition to this piperidine exerted an anxiolytic effect in the male rat. In both effects, the mechanism of action remains to be characterized.

Effects of a 90-min educational intervention for patients with insect venom allergy: a prospective controlled pilot study

BackgroundAnaphylactic sting reactions need a prompt management. A structured educational intervention for patients with insect sting allergy has not been implemented so far. The purpose of this study was to analyze the effects of a structured 90-min educational intervention for patients with insect sting allergy.MethodsPatients with an insect venom allergy were offered to participate in a structured 90-min group education (intervention group (IG)) or to attend a control group (CG). The patients’ subjective self-assurance in using the emergency medication, the willingness to always carry the emergency medication, the mental health status, absolute one-time willingness-to-pay (WTP) for complete cure, a disease knowledge assessment and a simulation test to examine the ability to manage an acute sting reaction were estimated at baseline (t0) and at follow-up (t1) as outcome parameters.Results55 patients participated in the IG (n = 25, 52.0% female, mean age 55.9 years) or the CG (n = 30, 56.7% female, mean age 52.0 years). Both arms showed a significant gain in self-assurance in using the emergency medication (IG: 6.1 at t0 vs. 8.6 at t1, p < 0.0001 and CG: 7.1 vs. 8.0, p = 0.0062) and ability to manage an acute sting reaction (IG: 6.7 vs. 11.4, p < 0.0001 and CG: 9.0 vs. 10.5, p = 0.0002) at t1. However, trained participants showed a significantly higher gain in the respective parameters. There were no significant changes regarding the remaining examined outcome parameters.ConclusionsPatients who are willing to invest 90 min in a patient education intervention benefit significantly by an increased subjective and objective empowerment to manage an acute sting reaction.

Cell-Penetrating Peptides Derived from Animal Venoms and Toxins.

Cell-penetrating peptides (CPPs) comprise a class of short polypeptides that possess the ability to selectively interact with the cytoplasmic membrane of certain cell types, translocate across plasma membranes and accumulate in the cell cytoplasm, organelles (e.g., the nucleus and mitochondria) and other subcellular compartments. CPPs are either of natural origin or de novo designed and synthesized from segments and patches of larger proteins or designed by algorithms. With such intrinsic properties, along with membrane permeation, translocation and cellular uptake properties, CPPs can intracellularly convey diverse substances and nanomaterials, such as hydrophilic organic compounds and drugs, macromolecules (nucleic acids and proteins), nanoparticles (nanocrystals and polyplexes), metals and radionuclides, which can be covalently attached via CPP N- and C-terminals or through preparation of CPP complexes. A cumulative number of studies on animal toxins, primarily isolated from the venom of arthropods and snakes, have revealed the cell-penetrating activities of venom peptides and toxins, which can be harnessed for application in biomedicine and pharmaceutical biotechnology. In this review, I aimed to collate examples of peptides from animal venoms and toxic secretions that possess the ability to penetrate diverse types of cells. These venom CPPs have been chemically or structurally modified to enhance cell selectivity, bioavailability and a range of target applications. Herein, examples are listed and discussed, including cysteine-stabilized and linear, α-helical peptides, with cationic and amphipathic character, from the venom of insects (e.g., melittin, anoplin, mastoparans), arachnids (latarcin, lycosin, chlorotoxin, maurocalcine/imperatoxin homologs and wasabi receptor toxin), fish (pardaxins), amphibian (bombesin) and snakes (crotamine and cathelicidins).

What Gastroenterologists Should Know About COVID-19 Vaccines

What Gastroenterologists Should Know About COVID-19 Vaccines

BEES AND WASPS VENOM TOXINS, ITS IMMUNE-ALLERGIC RESPONSES, DIAGNOSIS AND THERAPEUTICS

Present article explains insect toxins, its immune allergic, pharmaceutical and therapeutic effects. Insect venom glands generate enzymatic and non-enzymatic toxins and are inflicted by the stings. Insect’s envenomation are highly painful, inflamed and life-threatening. It causes breathing difficulties, bronchospasm, hypotension and arrhythmia, cardiopulmonary problems, and imposes allergic reactions. Wasp venom toxins generate strong T-cell responses in hypersensitivity patients and stimulate the production of IgE antibody molecules. Massive envenomations causes the death of victims due to the toxic effects of the venom toxins if clinical treatment is delayed. This article also emphasizes the role of natural and recombinant toxins for the development of highly sensitive immune-assays for diagnosis of allergen-specific tolerance, its early and delayed effects in patients to avoid fatal anaphylactic reactions. It also directs about the essentiality of immune diagnostics, vaccines and antiserum therapy in high population density regions where incidences of wasp and bee envenomations are more frequently occur. Venom immunotherapy can restore normal immunity against venom allergens and may also provide lifetime tolerance against venoms. This article highlights the major effects of insect venom allergens, its diagnosis and venom immunotherapy.

Anaphylaxis in middle-aged patients.

Age is one of the most important factors influencing the course of anaphylaxis: moreover, the frequency of elicitors of anaphylaxis is age-associated. We analyzed 8,465 anaphylactic episodes in adult patients in three age groups with a focus on patients in the middle-age group (35 – 65 years old). Insect venom was the most frequent trigger in this age group (51.2%) followed by drugs (22.8%) and food (17.3%). Severe reactions were observed in 40.1% of middle-aged patients and occurred more frequently in this age group than in patients below 35 years (27.6%) and less frequently than in patients over 65 years (55.6%). The symptoms and comorbidity profile also changed with age, most significantly regarding the increase in rates of concomitant cardiologic diseases and (severe) cardiovascular symptoms.

Disintegrin-Like Peptides Derived from Naturally-Occurring Proteins: A Proposed Adjunct Treatment for Cancer Therapy: A Commentary

Disintegrins constitute a group of small proteins or peptides (45-85 amino acids) that function as natural antagonists of integrin receptor-dependent cell activities. The integrins themselves comprise a superfamily of hetero-dimeric (alpha and beta chains) transmembrane cell surface receptors whose functions include cell adhesion, growth, migration, and angiogenesis. In contrast, the disintegrins comprise groups of two types of molecules, namely, a) short proteins or peptides comprising insect and animal venoms; and b) intrinsic sub domain sequence fragments or short motifs present on large mammalian metalloprotease enzymes. Certain disintegrins bind specifically to tri-amino acid sequences (RGD, LGD etc) located on integrins beta-1 and beta-3 chains of the hetero complex receptors. Binding at such sites can inhibit or block cell migration, angiogenesis, metastasis, and platelet aggregation. Recently, small disintegrin-like peptides from naturally-occurring proteins have likewise been reported to inhibit growth and adhesion functions associated with integrin-dependent cell activities. The present report describes examples of such disintegrin-like peptides and provides support for their proposed use in adjunct cancer therapy.

Benefits and limitations of sting challenge in hymenoptera venom allergy.

The prevalence of systemic reactions to hymenoptera stings is up to 7.5%. Venom-specific immunotherapy (VIT) is an established treatment for insect venom allergy. In order to monitor the allergic status and thus the success of the therapy, controlled sting challenge under VIT continues to be the gold standard. This review deals not only with useful indications and therapeutic consequences but also with critical aspects that should be considered when performing sting challenge.

Prick and intradermal skin tests in patients with severe hymenoptera sting allergy using commercial versus in-house allergen extracts.

Fire ant, honey bee, and wasp allergen extracts are useful in the diagnosis and treatment of severe Hymenoptera allergic patients. To evaluate the result of skin prick test (SPT) and intradermal test (ID) compared between local and commercial insect allergen extracts in patients with severe Hymenoptera sting allergy. SPT and ID using local and commercial insect allergen extracts were performed. Specific IgE (sIgE) to honey bee, wasp, and fire ant; component-resolved diagnosis (CRD); (rApi m1, rApi m2, rApi m3, rApi m5, rApi m10, rVes v5, rPol d5, and rVes v1); and, cross-reactive carbohydrate determinant (CCD) were performed. Twenty-seven patients were included. Twenty-five had anaphylaxis, and 2 had severe systemic skin reaction. Positive skin test (SPT and/or ID) result from local and commercial allergen extracts was 74% vs. 67% for fire ant, 48% vs. 59% for honey bee, and 52% vs. 74% for yellowjacket. Local and commercial allergen extracts showed substantial agreement for fire ant (k = 0.647, p = 0.001) and honey bee (k = 0.632, p = 0.001), and moderate agreement for wasp (k = 0.547, p = 0.001). When compared with sIgE subtracted with CCD and/or CRD, skin test results of local fire ant allergen extract showed higher sensitivity (87% vs. 67%), specificity (42% vs. 33%), and accuracy (67% vs. 52%) than commercial extract. Commercial honey bee and wasp showed higher sensitivity (62% vs. 50%, 85% vs. 65%) and accuracy (63% vs. 52%, 78% vs. 70%), respectively. SPT and ID with local or commercial insect venoms could help in confirming and/or identifying the causative insects.

COVID-19 vaccination and allergen immunotherapy (AIT) - A position paper of the German Society for Applied Allergology (AeDA) and the German Society for Allergology and Clinical Immunology (DGAKI).

Background: Vaccinations against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are intended to induce an immune response to protect against infection/disease. Allergen immunotherapy (AIT) is thought to induce a (different) immune response, e.g., to induce tolerance to allergens. In this position paper we clarify how to use AIT in temporal relation to COVID-19 vaccination. Four SARS-CoV-2 vaccines are currently approved in the EU, and their possible immunological interactions with AIT are described together with practical recommendations for use. Materials and methods: Based on the internationally published literature, this position paper provides specific recommendations for the use of AIT in temporal relation to a SARS-CoV-2 vaccination. Results: AIT is used in 1) allergic rhinitis, 2) allergic bronchial asthma, 3) insect venom allergy, 4) food allergy (peanut). Conclusion: For the continuation of an ongoing AIT, we recommend an interval of 1 week before and after vaccination for subcutaneous immunotherapy (SCIT). For sublingual immunotherapy (SLIT) and oral immunotherapy (OIT), we recommend taking them up to the day before vaccination and a break of 2 – 7 days after vaccination. Initiation of a new SCIT, SLIT, or OIT should be delayed until 1 week after the day of the second vaccination. For SCIT, we generally recommend an interval of ~ 1 week to COVID-19 vaccination.

Use of biologics in allergen immunotherapy.

Biologics are drugs that are derived or synthesized from biological sources. A particular class are recombinant monoclonal antibodies. Their targeted application against distinct molecules of intercellular communication is of significant relevance in the treatment of tumor, inflammatory, or allergic diseases. But also in the context of allergen immunotherapy (AIT) they can be of special value. This is exemplified by the anti-IgE antibody omalizumab, which allows to achieve allergen tolerance in patients suffering from severe allergic reactions and increased risk of AIT-induced anaphylaxis. Furthermore, omalizumab administration during AIT effectively lowers the rsik of allergic side effects. This is demonstrated by a variety of studies and case reports of patients suffering either form respiratory, food, or insect venom allergy. Besides a direct blocking of IgE-mediated effects, T-cellular immune mechanisms might also be involved. Another interesting option is the applcation of recombinant IgG antibodes directed against specific epitopes of an allergen. Similar to AIT-induced IgG antibodies they can prevent the binding of allergens to IgE-antibodes as well as the hereby elicited allergic reactions.

Crouching Tiger, Hidden Protein: Searching for Insecticidal Toxins in Venom of the Red Tiger Assassin Bug (Havinthus rufovarius).

Assassin bugs are venomous insects that prey on other arthropods. Their venom has lethal, paralytic, and liquifying effects when injected into prey, but the toxins responsible for these effects are unknown. To identify bioactive assassin bug toxins, venom was harvested from the red tiger assassin bug (Havinthus rufovarius), an Australian species whose venom has not previously been characterised. The venom was fractionated using reversed-phase high-performance liquid chromatography, and four fractions were found to cause paralysis and death when injected into sheep blowflies (Lucilia cuprina). The amino acid sequences of the major proteins in two of these fractions were elucidated by comparing liquid chromatography/tandem mass spectrometry data with a translated venom-gland transcriptome. The most abundant components were identified as a solitary 12.8 kDa CUB (complement C1r/C1s, Uegf, Bmp1) domain protein and a 9.5 kDa cystatin. CUB domains are present in multidomain proteins with diverse functions, including insect proteases. Although solitary CUB domain proteins have been reported to exist in other heteropteran venoms, such as that of the bee killer assassin bug Pristhesancus plagipennis, their function is unknown, and they have not previously been reported as lethal or paralysis-inducing. Cystatins occur in the venoms of spiders and snakes, but again with an unknown function. Reduction and alkylation experiments revealed that the H. rufovarius venom cystatin featured five cysteine residues, one of which featured a free sulfhydryl group. These data suggest that solitary CUB domain proteins and/or cystatins may contribute to the insecticidal activity of assassin bug venom.