Stinging insect vaccines: patient selection and administration of Hymenoptera venom immunotherapy.

Immunotherapy for prevention of allergic reactions to insect stings has a long history checkered by the use of whole body extracts for over 50 years, 24 the eventual development (25 years ago) of the first standardized extracts with specific Hymenoptera venom protein allergens, 38 and the refinement of arguably the most effective form of treatment available to allergists and their patients. 28 The appropriate clinical application of this remarkable treatment requires an understanding of the clinical patterns of reaction, the natural history of the disease, and the human immune response to insect venoms. The simple fact that whole body extracts were certified as being effective, even though they are no more effective than placebo, illustrates the importance of recognizing the distinction between natural history and therapeutic effect. Although the research of the past 20 years has revealed many of the markers and patterns of reactions that enable the statistical prediction of risk, there remains a fundamental deficiency in understanding that limits the ability to predict with precision which individuals will have a severe reaction to a sting. The current standard of practice in North America rests primarily on statistical observations that provide the framework for patient selection and for the methods of administration of venom immunotherapy. The risk of anaphylaxis occurs primarily with stinging insects of the order Hymenoptera. Insect bites by numerous species can cause local inflammation, swelling (including IgE-mediated reactions), and toxic systemic reactions to envenomation, but the occurrence of anaphylaxis from biting insects is rare. There are three families of Hymenoptera with clinical importance: bees (e.g., honeybees, bumblebees), vespids (e.g., yellow jackets, hornets, wasps), and fire ants (e.g., genus Soienopsis ). Exposure to these insects is affected by environmental and ecological changes. The predominant species of fire ants was imported inadvertently through Mobile, Alabama in the early part of the twentieth century and has rapidly become an increasing public health hazard in the southeast and southern United States. 4 The Africanized honeybee ("killer bee") is an aggressive hybrid resulting from an ill-advised experiment to enhance honey production. The danger from the Africanized honeybee stems from the numbers of stings because of swarm-and-attack behavior rather than any greater allergenicity or toxicity of their venom, which is in fact similar to that of other honeybees. The allergens in honeybee venom are immunochemically distinct from those of the vespid venoms (see article by Weber elsewhere in this issue). 41 The vespid venoms cross-react and contain essentially the same allergens. 36 The yellow jacket and hornet venoms are related so closely that 95% of vespid-allergic patients have positive skin tests to all three of the common vespid skin test preparations: yellow jacket, yellow hornet, and white-faced hornet. Polistes wasps are more distantly related to the other vespids, and only 50% of yellow-jacket–allergic patients have cross-reactive positive tests to wasp venom. Fire ant venoms are unique in that they contain minimal protein in a suspension of alkaloid toxins. The alkaloid component is the cause of the painful, sterile, and pustule characteristic of fire ant stings but does not cause allergic reactions. The allergenic proteins of fire ants are unique except for one that cross-reacts slightly with a vespid allergen. 37