Complement activation in wasp venom-induced acute kidney injury.

Previous studies have highlighted the significant role of complement activation in kidney injuries induced by rhabdomyolysis, intravascular hemolysis, sepsis, and ischemia-reperfusion. Nevertheless, the specific role and mechanism of complement activation in acute kidney injury (AKI) caused by wasp venom remain unclear. The aim of this study was to elucidate the specific complement pathway activated and investigate complement activation in AKI induced by wasp venom. In this study, a complement-depleted mouse model was used to investigate the role of complement in wasp venom-induced AKI. Mice were randomly categorized into control, cobra venom factor (CVF), AKI, and CVF + AKI groups. Compared to the AKI group, the CVF + AKI group showed improved pathological changes in kidneys and reduced blood urea nitrogen (BUN) levels. The expression levels of renal complement 3 (C3), complement 5 (C5), complement 1q (C1q), factor B (FB), mannose-binding lectin (MBL), and C5b-9 in AKI group were upregulated compared with the control group. Conversely, the renal tissue expression levels of C3, C5, C1q, FB, MBL, and C5b-9 were decreased in the CVF + AKI group compared to those in the AKI group. Complement activation occurs through all three pathways in AKI induced by wasp venom. Furthermore, complement depletion by CVF attenuates wasp venom-induced nephrotoxicity, suggesting that complement activation plays a primary role in the pathogenesis of wasp venom-induced AKI.

Field sting reactions in patients receiving Hymenoptera venom immunotherapy: real-life experience.

BACKGROUND: Hymenoptera stings can cause systemic allergic reactions (SARs) that are prevented by venom immunotherapy (VIT). Sting challenge tests or field stings are used to evaluate the outcome of VIT. OBJECTIVE: The aim of the study was to investigate the consequences of field stings in patients during or after completion of VIT, and to identify patients at higher risk. METHODS: Patients treated with VIT between 1995 and 2018 were retrospectively evaluated. Contacted patients were invited to the clinic and a questionnaire was conducted regarding the history of field stings. RESULTS: A total of 115 patients (F/M: 45/70, mean age: 38.5 ± 12 years) treated with VIT were included; 74/115 were contacted and asked about field stings after VIT cessation. A history of 73 field stings was reported in 38 patients, 25 of whom were treated with honeybee venom and 13 with common wasp venom. Eighteen of the reactions were SARs [8 with honeybees (1 grade-I, 6 grade-II, 1 grade-III) and 10 with common wasps (1 grade-I, 5 grade-II, 4 grade-III)]. There was no association between the severity of index reactions and field stings with either the honeybee or common wasp. The median duration of VIT was longer in patients showing no reaction than in patients with an SAR. Of the 7 patients on ACE inhibitors or beta-blockers, 1 asthmatic patient developed grade-II SAR due to field stings in the first year of VIT. CONCLUSIONS: This study confirms that VIT lasting at least 3 years is effective in preventing SARs after field stings.

Vespa velutina nigrithorax venom allergy: inhibition studies approach for the choice of specific immunotherapy.

Summary: Vespa velutina nigrithorax (VVN), commonly known as Asian wasp because endemic in Asia, represents an alien species in Europe. VVN can induce allergic reactions similar to those caused by other Hymenoptera and death after VVN stings, presumably due to fatal allergic reactions, has been reported. In the treatment of Hymenoptera venom hypersensitivity, specific immunotherapy (VIT) is highly effective. Currently, there is no specific available VIT for VVN, so it is relevant to assess if patients stung by VVN and showing allergic reactions could be treated with the Hymenoptera commercially available extracts Vespa crabro (VC) and Vespula spp (Vspp) or if they need the specific VIT with VVN venom extract. Methods. Four patients with a clinical history of systemic reactions after VVN sting were evaluated. Serum specific IgE were assayed quantitatively with an automated fluoro-enzyme immunoassay ImmunoCAP™ Specific IgE by Phadia™ 1000 System (Thermo Fisher Scientific, Uppsala, Sweden) for VC, Vspp and VVN. Cap inhibition assays were performed incubating serum samples with 200 µl of each venom at increasing concentrations and subsequently specific IgE against each of the venoms were determined in the samples by Phadia™ 250 System (Thermo Fisher Scientific, Uppsala, Sweden). Results. Our results suggested that both Vspp and VC venoms were able to inhibit the specific IgE for VVN, although the VC compared to the Vspp venom showed a higher inhibition. Conclusions. Our inhibition studies suggested that VIT with VC venom, nowadays when there is not specific available VIT for VVN, may be more effective than Vspp VIT in patients with VVN sting reactions.

Venom immunotherapy and difficulties encountered before and during immunotherapy: Double sensitization, systemic reactions, treatment with omalizumab, and high dose VIT.

BACKGROUND: Venom immunotherapy (VIT) is the most effective treatment method to prevent recurrent systemic reactions to Hymenoptera stings. In this study, the demographic characteristics of VIT patients, the success rates of VIT, the difficulties we encountered during VIT, and solutions for these difficulties in our clinic were presented. METHODS: We retrospectively analyzed patients with venom allergy who applied venom immunotherapy between 2013- 2020. Data on age, gender, Hymenoptera species with the first reaction, grade of the reaction, beekeeping history, skin prick and specific IgE and component results, double sensitization, blood groups, and reactions with VIT and/or sting during built-up and maintenance periods were recorded. RESULTS: A total of 73 patients were enrolled in the study. The median time from the first sting reaction to the application to the allergy outpatient clinic was 12 (0.5-24) months. The first sting reaction of 38 (52.1%) of the patients was with honey bees, and 24 (32.9%) were with wasps. Double positivity was present in 29 (40%) of the patients in prick results and 26 (36%) serologically. There was no correlation between the severity of first reactions and Apis Mellifera or Vespula prick diameters (p = 0.643; r = -0.056; p = 0.462; r = 0.089, respectively). High-dose VIT was administered to 4 patients. Omalizumab has been used as an alternative agent to achieve the maintenance dose in 2 patients with frequent systemic reactions during VIT. DISCUSSION: Most patients were able to tolerate VIT. Double positivity is one of the most common difficulties before VIT. In patients who develop systemic reactions in the VIT maintenance phase, a maintenance dose increase should be considered in the maintenance phase. Adding omalizumab does not seem to be a permanent solution in patients who develop a severe systemic reaction.

Adverse reactions in venom immunotherapy protocols: conventional versus ultra-rush.

BACKGROUND: Venom immunotherapy (VIT) is an effective treatment in the patients at high risk of anaphylaxis or life-threatening systemic reactions due to Hymenoptera venom allergy. But, systemic and large local reactions can be observed, especially during the build-up phase of VIT. We evaluated the safety of conventional and ultra-rush build-up protocols. MATERIALS AND METHODS: Two protocols in 71 patients (39 conventional and 32 ultra-rush protocols) with honeybee and wasp venom allergy were evaluated retrospectively. Patients were diagnosed and selected for VIT according to the criteria established by the European Academy of Allergy and Clinical Immunology. The severity of systemic reactions was evaluated according to the criteria of Mueller. RESULTS: Build-up phases were tolerated in 66.2% (n = 47) without any reaction. Allergic adverse reactions were observed in 33.8% (n = 24): large local reactions 22.5% (n = 16) and systemic reactions 11.3% (n = 8). There was no significant difference in the number of adverse reactions comparing patients receiving conventional and ultra-rush protocol. In addition, no association was found between allergic adverse reactions and the following factors: sex, previous systemic sting reactions, honeybee and wasp venom extract. CONCLUSION: We found that both protocols were tolerated in patients with honeybee and wasp venom allergy. Ultra-rush protocol will be preferred for patients and clinicians because of its advantages in terms of time and costs.KEY MESSAGESVIT is the only curative treatment method that reduces the risk of severe reactions after a bee sting and improves the quality of life in patients with Hymenoptera venom allergy.Ultra-rush VIT protocol has advantages such as few injection and time savings.Both ultra-rush and conventional VIT are safe treatments to prevent potentially life-threatening reactions in patients with honeybee and wasp venom allergy.

Review of venom immunotherapy at a regional tertiary paediatric centre.

AIM: Bee stings can result in allergic reactions, including anaphylaxis. Venom immunotherapy (VIT) is a definitive cure for bee venom allergy, but controversy surrounds whether accelerated protocols are safe in children. Our primary aim was to assess the safety profile of ultra-rush bee VIT compared with conventional bee VIT at a regional paediatric tertiary centre. We also sought to evaluate the impact of both approaches on time and resource use. METHODS: Data were collected retrospectively from 14 patients with bee venom allergy who were treated with ultra-rush or conventional bee VIT between 2013 and 2021 at John Hunter Children's Hospital. We compared VIT-associated adverse reactions and use of resources in both these groups. RESULTS: Overall, six patients received ultra-rush bee VIT and eight patients received conventional VIT. The ultra-rush group had a lower rate of systemic reaction (16%) compared with the conventional group (25%). One patient from the conventional group required adrenaline. Ultra-rush patients require fewer injections over a shorter time and fewer hospital visits to complete the protocol. Travel distance for families was significantly reduced. CONCLUSION: At our regional paediatric tertiary centre, ultra-rush bee VIT was a safe treatment option for children with bee venom allergy. It has many advantages over a conventional approach, especially for patients living in regional or remote areas.

Parasitoid wasp venom manipulates host innate behavior via subtype-specific dopamine receptor activation.

The subjugation strategy employed by the jewel wasp is unique in that it manipulates the behavior of its host, the American cockroach, rather than inducing outright paralysis. Upon envenomation directly into the central complex (CX), a command center in the brain for motor behavior, the stung cockroach initially engages in intense grooming behavior, then falls into a lethargic sleep-like state referred to as hypokinesia. Behavioral changes evoked by the sting are due at least in part to the presence of the neurotransmitter dopamine in the venom. In insects, dopamine receptors are classified as two families, the D1-like and the D2-like receptors. However, specific roles played by dopamine receptor subtypes in venom-induced behavioral manipulation by the jewel wasp remain largely unknown. In the present study, we used a pharmacological approach to investigate roles of D1-like and D2-like receptors in behaviors exhibited by stung cockroaches, focusing on grooming. Specifically, we assessed behavioral outcomes of focal CX injections of dopamine receptor agonists and antagonists. Both specific and non-specific compounds were used. Our results strongly implicate D1-like dopamine receptors in venom-induced grooming. Regarding induction of hypokinesia, our findings demonstrate that dopamine signaling is necessary for induction of long-lasting hypokinesia caused by brain envenomation.

Clinical manifestation of multiple wasp stings with details of whole transcriptome analysis: Two case reports.

INTRODUCTION: Multiple wasp stings is an emergency result from systemic reactions to the toxin with a wide range of manifestations, and we presented 2 patients with distinct clinical and transcriptomic findings. PATIENT CONCERNS: Two patients without systemic disease presented with nearly 90 painful papules after attacked by a swarm of wasps (Vespa basalis). DIAGNOSIS: Patient 1 was a 44-year-old healthy male whose clinical manifestations mainly comprised hemolysis, hepatic injury, rhabdomyolysis, and acute kidney injury. Patient 2 was a 49-year-old healthy female who presented with severe acute respiratory distress syndrome (ARDS) in addition to certain clinical manifestations that were also found in patient 1. We used ribo- nucleic acid sequencing (RNA-Seq) to characterize the inflammatory responses of 2 patients with distinct clinical manifestations after multiple wasp stings. INTERVENTIONS: Both 2 patients received 5 sessions of plasmapheresis, and patient-1 further received mechanical ventilation for 8 days as well as 8 sessions of hemodialysis until day 17. OUTCOMES: Both patients recovered uneventfully after the aforementioned management. We used RNA-Seq to demonstrate a largely regulated neutrophil-predominated immune response in patient 1. In patient 2, we found a profound neutrophilc response on week 1 and a robust neutrophilic as well as pro-inflammatory responses on week 2. Furthermore, we found increased expression of signals that were associated with renal system process on week 2. CONCLUSION: In conclusion, we report 2 patients who manifested with shared and distinct presentations after an attack by the same swarm of wasps. Both patients had hemolysis, rhabdomyolysis, hepatic injury and acute kidney injury, and 1 patient had ARDS. The whole transcriptomic analyses were consistent with the distinct clinical manifestation, and these results suggest the potential of RNA-Sequencing to disentangle complex inflammatory responses in patients with multiple wasp stings. Plasmapheresis and corticosteroid were administered to both patients and case 2 also underwent 8 sessions of hemodialysis.

Massive Vespa basalis stings induce an envenoming syndrome.

Envenoming syndrome induced by massive Vespa basalis stings is a critical condition. Severe systemic reaction may present with hemolytic activity and rhabdomyolysis, leading diffuse alveolar hemorrhage, adult respiratory distress syndrome, coagulopathy, and multiple organs failure. In severe envenoming syndrome population, extracorporeal membrane oxygenation (ECMO) may be considered for unstable hemodynamic status. However, few studies reported ECMO in venom-induced disseminated intravascular coagulation patients. Here, we provide a case presented with pulmonary hemorrhage due to multiple Vespa basalis stings tried to rescue by veno-arterial extracorporeal membrane oxygenation. We also highlight that early recognition of venom-induced disseminated intravascular coagulation by checking coagulation profile in high risk patients may prevent from poor outcome.

Ocular Lesions Other Than Stings Following Yellow-Legged Hornet (Vespa velutina nigrithorax) Projections, as Reported to French Poison Control Centers.

Importance: Since the accidental introduction of the yellow-legged hornet (Vespa velutina nigrithorax) in France in 2004, there have been reports of this insect unexpectedly projecting a liquid toward the human face, but ocular morbidity associated with this is unknown, to our knowledge. Objective: To describe a case series of ocular lesions after exposure to a liquid projection emitted by a hornet. Design, Setting, and Participants: This was an analysis of all cases of ocular exposure to a projection by a yellow-legged hornet (excluding stings in the eye) collected by French poison control centers between January 1, 2004, and December 31, 2019. Main Outcomes and Measures: Symptoms were evaluated, and a fluorescein eye stain test was used. Results: Twenty-nine cases were recorded (24 in male and 5 in female patients; median age, 40 [interquartile range, 11] years); the first occurred in 2009. Most cases (20 [80%]) were occupational exposure among professionals dealing with hornet nests (eg, firefighters, wasp exterminators). Symptoms consistent with conjunctivitis often resolved quickly after ocular decontamination, but 5 patients developed a periorbital edema, 2 experienced radiating neuropathic pain, and 2 experienced keratitis. Conclusions and Relevance: These findings suggest that the projection of a liquid into the eyes by the yellow-legged hornet presents a new risk to human health, but its precise nature remains to be determined. Ocular lesions had a favorable outcome. For professionals who deal with these insects, adaptation of the usual protections designed for native hymenopterans may be warranted.

Hymenoptera venom allergy among children in Italy: time for pediatricians to take action

Hymenoptera venom allergy (HVA) is one of the most frequent causes of anaphylaxis following a bee, vespid or ant sting. Real-life data regarding the management of HVA in children are lacking. To address this unmet need, we carried out a survey defining the current management of HVA in children among pediatric allergists in Italy. Educational investments on the improvement of the management of pediatric patients with HVA are urgently needed, and our analysis represents a relevant instrument in targeting a roadmap with this aim. The time for pediatric allergists to take action has come, and a task force from the Rare Allergic Diseases Commission of the Italian Society of Pediatric Allergy and Immunology is working on the topic to improve pediatricians' knowledge and optimize the care of these patients

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Comparison of Clinical Manifestations, Treatments, and Outcomes between Vespidae Sting and Formicidae Sting Patients in the Emergency Department in Taiwan.

BACKGROUND: Hymenopteran stings are the most common animal insult injury encountered in the emergency department. With increasing global spread of imported fire ants in recent decades, the rate of Formicidae assault has become a serious problem in many countries. Formicidae-associated injuries gradually increased in Taiwan in recent decades and became the second most common arthropod assault injury in our ED. The present study aimed at comparing the clinical characteristics of Formicidae sting patients with those of the most serious and common group, Vespidae sting patients, in an emergency department (ED) in Taiwan. METHODS: This retrospective study included patients who were admitted between 2015 to 2018 to the ED in a local teaching hospital in Taiwan after a Vespidae or Formicidae sting. Cases with anaphylactic reaction were further compared. RESULTS: We reviewed the records of 881 subjects (503 males, 378 females; mean age, 49.09 ± 17.62 years) who visited our emergency department due to Vespidae or Formicidae stings. A total of 538 (61.1%) were categorized into the Vespidae group, and 343 (38.9%) were sorted into the Formicidae group. The Formicidae group had a longer ED length of stay (79.15 ± 92.30 vs. 108.00 ± 96.50 min, p < 0.01), but the Vespidae group had more cases that required hospitalization (1.9% vs. 0.3%, p = 0.04). Antihistamines (76.8% vs. 80.2%, p < 0.01) were more frequently used in the Formicidae group, while analgesics were more frequently used in the Vespidae group (38.1% vs. 12.5%, p < 0.01). The Vespidae group had more local reactions, and the Formicidae group had more extreme, systemic, or anaphylactic allergic reactions. Creatine kinase was significantly higher in the Vespidae group with an anaphylactic reaction. Sting frequency in both groups exhibited the same positive associations with average temperature of the month and weekend days. CONCLUSION: Formicidae sting patients presented to the ED with higher rate allergic reactions and spent more time in the ED than Vespidae sting patients. However, Vespidae sting patients had more complications and higher rates of admission, especially with anaphylactic reaction. Laboratory data, especially creatine kinase data, were more valuable to check in Vespidae sting patients with an anaphylactic reaction in the ED. Both groups exhibited positive correlations with temperature and a higher rate on weekend days.

Cell death associated release of volatile organic sulphur compounds with antioxidant properties in chemical-challenged tobacco BY-2 suspension cultured cells.

The production of volatile organic compounds (VOCs) during programmed cell death (PCD) is still insufficiently studied and their implication in the process is not well understood. The present study demonstrates that the release of VOSCs with presumed antioxidant capacity (methanethiol, dimethylsulfide and dimethyldisulfide) accompanies the cell death in chemical-stressed tobacco BY-2 suspension cultured cells. The cells were exposed to cell death inducers of biotic nature mastoparan (MP, wasp venom) and camptothecin (CPT, alkaloid), and to the abiotic stress agent CdSO4. The VOCs emission was monitored by proton-transfer reaction mass spectrometry (PTR-MS). The three chemicals induced PCD expressing apoptotic-like phenotype. The identified VOSCs were emitted in response to MP and CPT but not in presence of Cd. The VOSCs production occurred within few hours after the administration of the elicitors, peaked up when 20-50 % of the cells were dead and further levelled off with cell death advancement. This suggests that VOSCs with antioxidant activity may contribute to alleviation of cell death-associated oxidative stress at medium severity of cell death in response to the stress factors of biotic origin. The findings provide novel information about cell death defence mechanisms in chemical-challenged BY-2 cells and show that PCD related VOSCs synthesis depends on the type of inducer.

Venom immunotherapy in patients with clonal mast cell disorders: IgG4 correlates with protection.

BACKGROUND: Patients with clonal mast cell disorders (cMCD), systemic mastocytosis (SM) and monoclonal mast cell activation syndrome (MMAS), represent an increased risk for Hymenoptera venom anaphylaxis (HVA). Lifelong venom immunotherapy (VIT) is recommended; however, its efficacy and safety are controversial. Hence, we sought to evaluate the efficacy and safety of VIT in HVA patients with cMCD. METHODS: A retrospective study was conducted among 46 patients with Vespula venom allergy who had experienced severe HVA, 32 cMCD (22 with SM and 10 with MMAS) and 14 controls. There were no differences between cMCD patients and controls in age (58 vs 66) and duration of VIT (47 vs 48 months), respectively. RESULTS: During VIT, 11 (34%) cMCD patients experienced adverse reactions (ARs) (7% in controls), including 1 anaphylaxis. There were 23 re-stings in 17 (53%) patients during VIT. Of episodes, four (17%) presented with anaphylaxis, 14 (60%) presented with local reaction, and five (23%) were asymptomatic. In 11 episodes (48%), the patient did not take epinephrine, of these 8 (73%) presented with local reaction, and 3 (27%) were asymptomatic. Patient-based protection from anaphylaxis was 76% (4/17) in cMCD vs. 100% in controls during VIT. The venom-specific IgG4 concentrations increased during VIT (P < .001) although tryptase and IgE were unaltered. CONCLUSION: Both safety and efficacy of VIT in cMCD patients were slightly reduced than controls. Severe ARs were rare. The elevated IgG4 levels may be a biomarker for efficacy of VIT in cMCD patients, as it correlates with protection from re-stings.

Hymenoptera Venom Allergy: How Does Venom Immunotherapy Prevent Anaphylaxis From Bee and Wasp Stings?

Hymenoptera stings may cause both local and systemic allergic reactions and even life threatening anaphylaxis. Along with pharmaceutical drugs and foods, hymenoptera venom is one of the most common causes of anaphylaxis in humans. To date, no parameter has been identified that may predict which sensitized people will have a future systemic sting reaction (SSR), however some risk factors, such as mastocytosis and age >40 years are known. Venom immunotherapy (VIT) is the most effective method of treatment for people who had SSR, which is shown to be effective even after discontinuation of the therapy. Development of peripheral tolerance is the main mechanism during immunotherapy. It is mediated by the production of blocking IgG/IgG4 antibodies that may inhibit IgE dependent reactions through both high affinity (FcεRI) and low affinity (FcεRII) IgE receptors on mast cells, basophils and B cells. The generation of antigen specific regulatory T cells produces IL-10 and suppresses Th2 immunity and the immune responses shift toward a Th1-type response. B regulatory cells are also involved in the production of IL-10 and the development of long term immune tolerance. During VIT the number of effector cells in target organs also decreases, such as mast cells, basophils, innate type 2 lymphocytes and eosinophils. Several meta-analyses and randomized controlled studies have proved that VIT is effective for preventing SSR to a sting and improves the quality of life. In this review, the risk of SSR in venom allergy and how VIT changed this risk are discussed.

Study of mastoparan analog peptides against Candida albicans and safety in zebrafish embryos (Danio rerio).

Aim: In this work, mastoparan analog peptides from wasp venom were tested against Candida albicans and safety assays were performed using cell culture and model zebrafish. Materials & methods: Minimal inhibitory concentration was determined and toxicity was performed using human skin keratinocyte and embryo zebrafish. Also, permeation of peptides through embryo chorion was performed. Results: The peptides demonstrated anti-C. albicans activity, with low cytotoxicity and nonteratogenicity in Danio rerio. The compounds had different permeation through chorion, suggesting that this occurs due to modifications in their amino acid sequence. Conclusion: The results showed that the studied peptides can be used as structural study models for novel potential antifungal agents.

Pharmacological Characterization of Mouse Hind Paw Edema Induced by Parachartergus fraternus Venom.

Stings from the wasp Parachartergus fraternus occur throughout Latin America, and edema followed by pain is the main symptom presented by victims. This often limited inflammatory event has not been characterized for this species. In this work, we identified the mechanisms and possible mediators involved in this response. P. fraternus venom (100, 200, and 400 µg/kg) was injected into the hind paws of mice, and edema was evaluated at intervals of 10 min for up to 60 min and at 120, 240, and 1440 min using a digital plethysmometer. The peak of edema was observed at 10 min with a dose of 200 µg/kg. A reduction in edema was observed with indomethacin (58.1%), celecoxib (44.5%), MK886 (30.8%), and dexamethasone (53.2%). Loratadine, cimetidine, and cyproheptadine treatment reduced the edema by 54.2%, 63.9%, and 84.4%, respectively, compared with the control. Captopril and L-NAME inhibited 42.5% and 69.8%, respectively, of the edema. These results showed that the edema induced in mice by P. fraternus venom occurs early and is mediated by arachidonic acid derivatives, vasoactive amines, and nitric oxide. Together, these mediators amplify the inflammatory process, with emphasis on histamine and serotonin in triggering the edematogenic response, being more effective the use of cyproheptadine in the therapeutic approach.

[Hymenoptera venom allergy]. / Insektengiftallergie: Die am häufigsten zum Tode führende Anaphylaxie.

Allergic reactions caused by sting of honeybees or wasps are very often and make also very severe anaphylactic reaction, up to 3,5 % of population. Mostly sting reactions are dependent to IgE induced reactions type I.Established are history, skin tests and specific IgE antibodies. Recombinant antibodies complete diagnostics in special cases. Specific immunotherapy is recommended as a very successful therapy in treating allergies due to honeybees and wasps. Many protocols are established, the standard maintenance dose is 100 mg. The hyposensitization is very successful with rates of nearly 100 % success. In most times a dose of 100 mg is sufficient, in some cases the dose must be increased to 200 mg. In most patients immunotherapy can be stopped after 3-5 years. Sting challenge tests should be done for proving the efficiency of immunotherapy. Many patients after immunotherapy have an improved live quality after sting provocations.