Drug and Venom Allergy in Mastocytosis.

Patients with mastocytosis have an increased risk for mast cell activation events including anaphylaxis when exposed to certain drugs and Hymenoptera venom. Hypotension and cardiovascular collapse without skin or other systemic manifestations can occur after Hymenoptera stings, during the perioperative period, and after exposure to nonsteroidal ntiinflammatory drugs, opioids, and other mast cell activating medications, including vancomycin and quinolones. This chapter reviews the epidemiology, mechanisms, diagnosis, management, and treatment options for Hymenoptera venom and drug-induced reactions in patients with mastocytosis.

Hymenoptera Venom Allergy and Anaphylaxis.

Hymenoptera stings can induce allergic and occasionally fatal reactions, and are responsible for significant morbidity and deterioration in health-related quality of life. The diagnostic work-up must consider the medical history of patients, in the context of venom allergy epidemiology and Hymenoptera taxonomy, and the clinical manifestations of the reactions, to channel the available in vivo and in vitro tests towards the most accurate diagnosis and the consequent appropriate management, also considering the risk profile of the patients on a precision-medicine approach. All these aspects are covered by this work that aims at providing an up-to-date review to increase the awareness of this topic among interested stakeholders, like healthcare professionals and political decision makers, who can contribute to the proper immediate and long-term management of venom allergy and anaphylaxis.

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.

A genetically engineered Plasmodium falciparum parasite vaccine provides protection from controlled human malaria infection.

Genetically engineered live Plasmodium falciparum sporozoites constitute a potential platform for creating consistently attenuated, genetically defined, whole-parasite vaccines against malaria through targeted gene deletions. Such genetically attenuated parasites (GAPs) do not require attenuation by irradiation or concomitant drug treatment. We previously developed a P. falciparum (Pf) GAP with deletions in P52, P36, and SAP1 genes (PfGAP3KO) and demonstrated its safety and immunogenicity in humans. Here, we further assessed safety, tolerability, and immunogenicity of the PfGAP3KO vaccine and tested its efficacy against controlled human malaria infection (CHMI) in malaria-naïve subjects. The vaccine was delivered by three (n = 6) or five (n = 8) immunizations with ~200 PfGAP3KO-infected mosquito bites per immunization. PfGAP3KO was safe and well tolerated with no breakthrough P. falciparum blood stage infections. Vaccine-related adverse events were predominately localized urticaria related to the numerous mosquito bites administered per vaccination. CHMI via bites with mosquitoes carrying fully infectious Pf NF54 parasites was carried out 1 month after the last immunization. Half of the study participants who received either three or five PfGAP3KO immunizations remained P. falciparum blood stage negative, as shown by a lack of detection of Plasmodium 18S rRNA in the blood for 28 days after CHMI. Six protected study participants received a second CHMI 6 months later, and one remained completely protected. Thus, the PfGAP3KO vaccine was safe and immunogenic and was capable of inducing protection against sporozoite infection. These results warrant further evaluation of PfGAP3KO vaccine efficacy in dose-range finding trials with an injectable formulation.

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.

Venom chemistry underlying the painful stings of velvet ants (Hymenoptera: Mutillidae).

Velvet ants (Hymenoptera: Mutillidae) are a family of solitary parasitoid wasps that are renowned for their painful stings. We explored the chemistry underlying the stings of mutillid wasps of the genus Dasymutilla Ashmead. Detailed analyses of the venom composition of five species revealed that they are composed primarily of peptides. We found that two kinds of mutillid venom peptide appear to be primarily responsible for the painful effects of envenomation. These same peptides also have defensive utility against invertebrates, since they were able to incapacitate and kill honeybees. Both act directly on cell membranes where they directly increase ion conductivity. The defensive venom peptides of Dasymutilla bear a striking similarity, in structure and mode of action, to those of the ant Myrmecia gulosa (Fabricius), suggesting either retention of ancestral toxins, or convergence driven by similar life histories and defensive selection pressures. Finally, we propose that other highly expressed Dasymutilla venom peptides may play a role in parasitisation, possible in delay or arrest of host development. This study represents the first detailed account of the composition and function of the venoms of the Mutillidae.

Thymoquinone ameliorates Pachycondyla sennaarensis venom-induced acute toxic shock in male rats.

BACKGROUND: For many decades, the sting of Samsun ant (Pachycondyla sennaarensis) has been a serious clinical challenge for the people living in some of the major Middle East and Asian countries. In the present study, the therapeutic potential of Nigella sativa derived plant extract component, thymoquinone (TQ) has been tested against the Samsun ant venom (SAV) at the toxic dose in the rats. METHODS: The adult male rats were divided into four groups (n = 10): control, SAV treated, SAV + TQ treated and TQ alone treated. It was found that the sub-lethal dose of SAV alters not only many of the kidney and liver function markers but also induces oxidative stress in the animals. Moreover, the SAV also disturbs various immunological parameters including expression of PMNs, CD-80, CD-86, interleukins and other cytokines compromising the affected organism towards mild to severe allergic reactions including life-risking anaphylaxis. RESULTS: The plant extract, TQ, effectively restores many of the biochemical and oxidative stress parameters comparable to the normal concomitant with improving the immunological aspects that might attributive in relieving from SAV-induced toxicity and allergic reactions in the affected organism to a greater extent. CONCLUSION: Hence, TQ has an excellent antidote property against SAV-induced toxicities in vivo. Although the study is a vivid indication of the potential therapeutic potential of TQ against the SAV induced in vivo toxicity, yet the actual mechanism of interaction translating the toxicity amelioration warrants further investigations.

Ocular injury from the venom of the Southern walkingstick.

PURPOSE: To report a case of severe conjunctival and corneal epithelial defects resulting from exposure to the venom of the Southern walkingstick, Anisomorpha buprestoides. DESIGN: Case report. INTERVENTION: The patient was treated with cyclopentolate 1% and underwent daily examinations until the corneal and conjunctival epithelial defects resolved. MAIN OUTCOME MEASURE: Resolution of corneal and conjunctival epithelial defects. RESULTS: The corneal and conjunctival epithelial defects slowly resolved over 6 days. Visual acuity improved to 20/20 in the affected eye. No residual corneal scarring was evident. CONCLUSIONS: Slowly resolving corneal and conjunctival epithelial defects can occur from direct contact with the venom from the Southern walkingstick, A. buprestoides; therefore, this insect should be approached with caution.