Summary

Solenopsis invicta, the red imported fire ant, is one of the most notorious invasive ant species worldwide with a rapidly expanding geographical range, and occurs in high densities in urban, agricultural, and non-agricultural areas. Aggressive foragers, worker fire ants will rapidly swarm and repeatedly sting any human or animal with which they come into contact. In humans, injection of the venom results in the formation of a white fluid-filled pustule or blister at the site of the sting approximately one day after the attack, a pathognomonic symptom characteristic only of fire ants. Protein allergens within the venom can elicit reactions ranging from an immediate localized burning sensation with dermal wheal and flare responses, to painful large local reactions characterized by pruritus, erythema, and edema lasting 24‒72 hours. Serious systemic allergic reactions resulting in life-threatening anaphylaxis have been reported for between 0.6% to 16% of individuals stung by fire ants, resulting in at least 80 fatalities, most of which were caused by fewer than five stings. Four allergenic molecules have been characterized to date from S. invicta venom, with variable degrees of cross-reactivity to homologs in other Solenopsis species as well as with venom homologs from other Hymenoptera, insect, and arachnid species.

Clinical Relevance

The lower body is the most frequent site of a stinging attack by S. invicta. Infants, the elderly, and individuals with limited mobility may be at particular risk of being stung by numerous fire ants if they cannot move away from the threat.

One sting from S. invicta delivers between 0.04‒0.11 µl of venom and 10‒100 ng of protein, however, in practice multiple stings are often received as worker ants swarm together in an attack. The venom of S. invicta is composed of 95% water-insoluble cytotoxic alkaloids and 5% aqueous proteins. In humans, injection of the alkaloid component results in the formation of a white fluid-filled pustule or blister at the site of the sting approximately one day after the attack, a pathognomonic symptom characteristic only of fire ants. Protein allergens can elicit reactions ranging from an immediate localized burning sensation with dermal wheal and flare responses, to painful large local reactions characterized by pruritus, erythema, and edema lasting 24‒72 hours.

Anecdotal reports suggest some individuals may be stung hundreds of times without developing systemic symptoms, however, for hypersensitized individuals, a single sting can elicit anaphylaxis with flushing, generalized urticaria, angioedema, laryngeal edema, bronchospasm, or loss of consciousness. Serious systemic allergic reactions resulting in life-threatening anaphylaxis have been reported for between 0.6% to 16% of individuals stung by fire ants, resulting in at least 80 fatalities. A survey of 29,300 physicians in the United States reported 83 fatal and two near-fatal fire ant sting reactions, with most deaths caused by fewer than five stings.

Stings can also trigger serum sickness, nephrotic syndrome, seizures, and worsening of pre-existing cardiopulmonary disease. Allergic reactions to fire ant stings have been reported by previously sensitized individuals as well as by non-fire ant-sensitized subjects who have documented sensitivity to yellow jacket (Vespula spp.) venom.

In the south-eastern USA, over 40 million people live in areas infested by S. invicta and an estimated 14 million people (35%) are stung every year. In 1998 in the state of South Carolina alone, one survey of 1,286 medical practitioners estimated that 600,000 cases of imported fire ant attack resulted in 33,000 people seeking medical treatment (94 people per 19,000 population), of whom 660 (1.9 per 10,000 population) were treated for anaphylaxis. In Taiwan, a recent observational study of 3,819 people stung by S. invicta reported that 21.8% (n=834) developed wheal and flare reactions, 7.5% (n=288) sought medical care, 2.78% (n=106) exhibited anaphylactic shock, and 0.55% (n=21) developed severe cellulitis and urticaria.

Cross-Reactivity

Variable degrees of cross-reactivity have been reported for individuals with venom from Solenopsis species as well as with venoms from other Hymenoptera.

In a cohort of 450 patients seeking medical treatment for insect allergy in West Bengal (India), skin prick tests (SPT) identified multiple sensitivities to a variety of insects including S. invicta (84.59%, n=313), common black ant (Lasius niger: 87.62%, n=324), honey bee (Apis cerana indica: 67.02%, n=248), mosquito (Aedes aegypti: 66.67%, n=247), and common wasp (Vespula vulgaris: 30.27%, n=112) [LAH20]. In this study, only 13% of patients showed single sensitivity towards fire ant only, while 45% of patients were cross-sensitized to black ant, fire ant, and honey bee.

In a survey of 49 patients who developed systemic allergic reactions to the imported fire ant, five individuals had associated hypersensitivity to other insects including deer fly (n=1), saddleback caterpillar (n=1), spider (n=1), and bee and wasp (n=2). In another survey, 36% (4/11) patients with scorpion venom allergy (Centruroides vittatus) had a history of anaphylaxis with positive SPT to imported fire ant venom, and a further two individuals had a history of large local reactions.

Sol i 1 shares some immunologic cross-reactivity with phospholipase vespid venoms, whereas the structure of Sol i 2 is not related to any other known proteins and does not cross-react with bee or vespid phospholipases. Sol i 3 shares between 44 to 50% identity with Ag5 molecules from yellow jacket (Vespula spp.), Dolichovespula spp., and hornet (Vespa spp.), but does not exhibit consistent immunologic cross-reactivity with vespid Ag5 allergens. Sol i 4 shares 35% identity with Sol i 2 but no immunologic cross-reactivity.

Reactions to stings from any fire ant are likely to cause sensitization to other fire ant species. Sol i 1 and Sol i 3 from S. invicta are highly cross-reactive with Sol r 1 and Sol r 3, respectively, from S. richteri (the black imported fire ant). In addition, Sol i 2 has 78.2% and 72.3% amino acid sequence homology with Sol r 2 (S. richteri) and Sol gem 2 (S. geminata, a tropical fire ant native to Thailand), respectively.