Fire Ant Poisoning

Injury MONDO:0100341 Pathograph 22 Show in embeddings browser poisoning

Fire ant poisoning is the acute injury produced when a Solenopsis worker ant anchors itself with its jaws and injects venom through an abdominal stinger, often repeatedly. Two mechanisms run in parallel from the same sting and account for the whole clinical range. The venom is overwhelmingly water-insoluble piperidine alkaloids, which are directly cytotoxic and produce immediate burning pain, a wheal, and the characteristic sterile pustule without any prior sensitization. A much smaller protein fraction carries the allergens Sol i 1 to Sol i 4, which drive IgE-mediated sensitization; on re-exposure a sensitized person can develop urticaria, airway compromise, or anaphylactic shock. The alkaloid branch is near-universal and self-limited; the protein branch is uncommon and is what kills.

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1
Mappings
2
Definitions
8
Pathophys.
13
Phenotypes
22
Pathograph
3
Medical Actions
2
Subtypes
1
Differentials
7
References
1
Deep Research
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Classifications

Harrison's Part
POISONING ENVENOMATION IMMUNE RHEUMATOLOGIC
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Mappings

MONDO
MONDO:0100341 fire ant poisoning
skos:exactMatch MONDO
Primary MONDO disease identifier for fire ant poisoning.
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Definitions

2
Clinical case definition for fire ant poisoning
Fire ant poisoning is an acute, exposure-dependent sting injury in which Solenopsis venom is injected into skin, producing immediate local alkaloid toxicity and, in a sensitized minority, an IgE-mediated systemic allergic reaction. It is not an inherited disorder and requires no host genotype.
CASE_DEFINITION Disease-level framing covering both the direct-toxicity and allergic routes
Show evidence (2 references)
PMID:30258210 SUPPORT BACKGROUND Human Clinical
"Immediate effects of the stings are mainly caused by a major (>95%) fraction of toxic alkaloids, but the later allergic responses"
Supports the two-mechanism definition by separating immediate alkaloid-driven effects from the later protein-driven allergic response.
PMID:42302087 SUPPORT Human Clinical
"When a RIFA nest is disturbed, the workers rapidly swarm out to attack the intruder using their stings and venom"
Supports that the necessary cause is contact with and venom injection by a stinging fire ant.
Practical diagnostic definition for fire ant sting reaction
Diagnosis is clinical, from the exposure history plus the characteristic lesion evolution. Where a biopsy is taken, a superficial and deep neutrophilic infiltrate with basophilic collagen degeneration supports the diagnosis even when the sterile pustule is absent.
DIAGNOSTIC_CRITERIA Clinical and histopathologic recognition of a fire ant sting reaction
Show evidence (2 references)
PMID:28873251 SUPPORT Human Clinical
"Skin reactions to the sting of the imported fire ant have characteristic clinicopathological features."
Supports that the sting reaction is clinically and histopathologically recognizable.
PMID:28873251 SUPPORT Human Clinical
"the main features were a superficial and deep dermal, perivascular, periadnexal and interstitial infiltrate consisting of neutrophils, with basophilic degeneration of the collagen"
Supports the specific histopathologic pattern used to support the diagnosis.
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Subtypes

2
Local sting reaction (direct alkaloid toxicity)
The near-universal form. Piperidine alkaloids injected into skin are directly cytotoxic, producing immediate burning pain and itching, a wheal, and a characteristic sterile pustule over roughly 24 hours. No prior sensitization is required, and large local reactions can persist up to 72 hours.
Show evidence (2 references)
PMID:42302087 SUPPORT Human Clinical
"The typical local reactions following RIFA stings are itching and burning pain, accompanied by redness and the development of raised wheals and white pustules at the sting site, followed by IgE-mediated urticarial and erythematous reactions"
Supports the local reaction as the typical presentation, and separates it from the subsequent IgE-mediated component.
PMID:42302087 SUPPORT Human Clinical
"56% of stung individuals experience noticeable localized reactions, whereas only 0.5-2% exhibit systemic allergy"
Supports that localized reactions dominate numerically over systemic allergy by roughly two orders of magnitude.
Fire ant venom anaphylaxis (IgE-mediated systemic reaction)
The uncommon but life-threatening form. In a person sensitized to the venom protein allergens, re-exposure triggers IgE-dependent mast cell activation, producing generalized urticaria, angioedema, airway compromise, or circulatory collapse. Systemic mastocytosis is a major risk factor, and in that group the reaction is frequently misdiagnosed and undertreated.
Show evidence (2 references)
PMID:40230786 SUPPORT Human Clinical
"Fire ant and flying Hymenoptera-venom anaphylaxis prevalence in the general population was 0.048% and 0.083%, respectively."
Supports fire ant venom anaphylaxis as a measurable distinct clinical entity with its own population prevalence.
PMID:40230786 SUPPORT Human Clinical
"Fire ant-venom anaphylaxis in systemic mastocytosis is frequently misdiagnosed and not treated with epinephrine."
Supports that the systemic form is underrecognized and undertreated in the highest-risk host group.
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Pathophysiology

8
Fire ant sting and venom deposition in skin
A worker ant anchors with its mandibles and injects venom through an abdominal stinger, usually several times. The injected volume is small, with only 10 to 100 ng of protein per sting, but the venom is overwhelmingly alkaloid by mass and both fractions are delivered together into the superficial skin.
response to toxic substance GO:0009636 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased response to toxic substance (GO:0009636). GO:0009636 is a biological process from the Gene Ontology.
skin of body UBERON:0002097 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skin of body (UBERON:0002097). UBERON:0002097 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Piperidine alkaloid cytotoxic injury to skin The dominant alkaloid fraction injures cells at the sting site directly.
Venom protein antigen presentation and type 2 sensitization In parallel, the minor protein fraction is taken up and processed by antigen-presenting cells.
Show evidence (2 references)
PMID:42302087 SUPPORT Human Clinical
"When a RIFA nest is disturbed, the workers rapidly swarm out to attack the intruder using their stings and venom"
Directly supports venom injection by swarming workers as the initiating event.
PMID:37624246 SUPPORT REVIEW SYNTHESIS Other
"fire ant venoms are characterized by a high proportion of water-insoluble alkaloids and a small number of water-soluble proteins"
Supports that the deposited venom is predominantly alkaloid with a minor protein fraction, which is what gives the disease its two branches.
Piperidine alkaloid cytotoxic injury to skin
The piperidine alkaloids, named solenopsins, make up over 95% of the venom and are directly cytotoxic. In vitro they killed dendritic cells at 10 micrograms per millilitre, which is why the authors concluded the alkaloids are not the immunogenic component. This cytotoxicity is the basis of the immediate burning pain and local injury, and it requires no immune memory.
keratinocyte CL:0000312 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves keratinocyte (CL:0000312). CL:0000312 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
skin epidermis UBERON:0001003 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skin epidermis (UBERON:0001003). UBERON:0001003 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Neutrophilic dermal infiltration and collagen degeneration Local cytotoxic injury recruits a dense neutrophilic infiltrate and degenerates dermal collagen.
Pruritus Local alkaloid injury produces the immediate itching that is the most frequently reported symptom.
Pain The same local alkaloid injury produces immediate burning pain.
Erythema Local injury and the accompanying inflammatory response produce redness at the sting site.
Show evidence (2 references)
PMID:30258210 SUPPORT In Vitro
"The venom alkaloids proved extremely cytotoxic even at 10"
Directly supports marked cytotoxicity of the venom alkaloid fraction in cell culture.
PMID:37624246 SUPPORT REVIEW SYNTHESIS Other
"These piperidine alkaloids were commonly named solenopsins"
Establishes the identity of the alkaloid class responsible for the direct toxicity.
Neutrophilic dermal infiltration and collagen degeneration
Biopsies taken in a clinical setting show a superficial and deep dermal infiltrate of neutrophils in perivascular, periadnexal and interstitial distribution, accompanied by basophilic degeneration of dermal collagen. This pattern is itself diagnostically useful even when the pustule is absent.
neutrophil CL:0000775 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neutrophil (CL:0000775). CL:0000775 is a cell type from the Cell Ontology.
inflammatory response GO:0006954 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased inflammatory response (GO:0006954). GO:0006954 is a biological process from the Gene Ontology.
dermis UBERON:0002067 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in dermis (UBERON:0002067). UBERON:0002067 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Sterile subepidermal pustule formation The neutrophilic infiltrate organizes into a subepidermal pustule over about 48 hours.
Show evidence (1 reference)
PMID:28873251 SUPPORT Human Clinical
"the main features were a superficial and deep dermal, perivascular, periadnexal and interstitial infiltrate consisting of neutrophils, with basophilic degeneration of the collagen"
Directly supports the neutrophilic infiltrate and collagen degeneration as the tissue-level lesion.
Sterile subepidermal pustule formation
The characteristic lesion is a sterile subepidermal pustule sitting over a wedge-shaped zone of degenerated dermal collagen. It was present in half of the retrospectively reviewed biopsies, so its absence does not exclude the diagnosis.
neutrophil CL:0000775 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves neutrophil (CL:0000775). CL:0000775 is a cell type from the Cell Ontology.
skin epidermis UBERON:0001003 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in skin epidermis (UBERON:0001003). UBERON:0001003 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Pustule The lesion presents clinically as the white pustule characteristic of a fire ant sting.
Skin vesicle Earlier or less developed lesions are recorded clinically as vesicles.
Show evidence (1 reference)
PMID:28873251 SUPPORT Human Clinical
"A subepidermal pustule was noted in half of the cases."
Supports the pustule as a characteristic but not invariable finding on biopsy.
Venom protein antigen presentation and type 2 sensitization
The minor water-soluble protein fraction carries the allergens Sol i 1 to Sol i 4. These proteins directly activate dendritic cells, upregulating MHC class II and the costimulatory molecule CD86, which licenses antigen presentation to naive T cells and a type 2 helper response with IL-4 production. The venom proteins did this without any added adjuvant, and themselves acted as an adjuvant for an unrelated antigen.
dendritic cell CL:0000451 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves dendritic cell (CL:0000451). CL:0000451 is a cell type from the Cell Ontology. T-helper 2 cell CL:0000546 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves T-helper 2 cell (CL:0000546). CL:0000546 is a cell type from the Cell Ontology.
antigen processing and presentation of exogenous peptide antigen via MHC class II GO:0019886 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased antigen processing and presentation of exogenous peptide antigen via MHC class II (GO:0019886). GO:0019886 is a biological process from the Gene Ontology. type 2 immune response GO:0042092 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased type 2 immune response (GO:0042092). GO:0042092 is a biological process from the Gene Ontology.
Downstream
Venom-specific IgE class switching The type 2 response drives B cell class switching to venom-specific IgE.
Show evidence (3 references)
PMID:30258210 SUPPORT PRIMARY RESULT In Vitro
"the venom proteins elicited an activation response, as shown by the upregulation of MHCII and CD86"
Directly supports dendritic cell activation by venom proteins, measured as MHC class II and CD86 upregulation.
PMID:30258210 SUPPORT PRIMARY RESULT Model Organism
"Based on eosinophil recruitment and production of Th2 cytokines, we hereby establish that fire ant proteins per se can lead to an allergic response"
Supports that the venom proteins alone are sufficient to drive a type 2 allergic response.
PMID:37624246 SUPPORT REVIEW SYNTHESIS Other
"four worker allergens have been isolated and characterized: Sol i 1, Sol i 2, Sol i 3, and Sol i 4"
Establishes the identity of the four characterized venom protein allergens driving sensitization.
Venom-specific IgE class switching
Activated B cells undergo clonal expansion and mature into IgE-secreting plasma cells producing antibody specific for the venom allergens. The sensitization rate to fire ant venom exceeds 90% in colonized regions, far above sensitization to other stinging Hymenoptera, so this state is common while anaphylaxis remains uncommon.
B cell CL:0000236 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves B cell (CL:0000236). CL:0000236 is a cell type from the Cell Ontology.
immunoglobulin production GO:0002377 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased immunoglobulin production (GO:0002377). GO:0002377 is a biological process from the Gene Ontology.
Downstream
Mast cell arming by venom-specific IgE Secreted allergen-specific IgE binds the high-affinity receptor on peripheral mast cells.
Show evidence (1 reference)
PMID:40230786 SUPPORT Human Clinical
"the sensitization rate to FA venom can be >90% in colonized regions and is higher than sensitization to other stinging Hymenoptera"
Supports that venom sensitization is near-universal in colonized regions, which is what makes the gap between sensitization and clinical anaphylaxis important.
Mast cell arming by venom-specific IgE
Venom-specific IgE occupies the high-affinity receptor on peripheral mast cells. This is the state that converts a subsequent ordinary sting into a potentially fatal event, and it is what whole-body extract immunotherapy acts on.
mast cell CL:0000097 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves mast cell (CL:0000097). CL:0000097 is a cell type from the Cell Ontology.
Downstream
IgE-mediated mast cell activation on re-exposure Armed mast cells are primed to degranulate when venom antigen is encountered again.
Show evidence (1 reference)
PMID:30258210 SUPPORT INDIRECT Model Organism
"activated B cells mature into IgE-secretory plasma cells, and the secreted allergen-specific IgE bind to peripheral mast-cells"
States that secreted allergen-specific IgE binds peripheral mast cells, which is this node. Graded INDIRECT because it is the authors' hypothesized scheme rather than a reported measurement.
IgE-mediated mast cell activation on re-exposure
On a later sting, venom antigen cross-links IgE on armed mast cells and basophils, releasing mediators that produce acute vascular permeability, generalized urticaria and, when the reaction is systemic, airway obstruction or circulatory collapse. Eosinophil recruitment driven by eotaxin follows at the sting site.
mast cell CL:0000097 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves mast cell (CL:0000097). CL:0000097 is a cell type from the Cell Ontology. eosinophil CL:0000771 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves eosinophil (CL:0000771). CL:0000771 is a cell type from the Cell Ontology.
mast cell activation GO:0045576 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased mast cell activation (GO:0045576). GO:0045576 is a biological process from the Gene Ontology. eosinophil chemotaxis GO:0048245 ↑ INCREASED Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves increased eosinophil chemotaxis (GO:0048245). GO:0048245 is a biological process from the Gene Ontology.
Downstream
Urticaria Mediator release produces generalized itching, rash and wheals beyond the sting site.
Venom-induced anaphylaxis A systemic mediator release presents as venom-induced anaphylaxis.
Laryngeal edema Mediator-driven swelling of the upper airway threatens obstruction.
Anaphylactic shock Severe systemic mediator release causes circulatory collapse.
Show evidence (2 references)
PMID:30258210 SUPPORT PRIMARY RESULT Model Organism
"venom proteins per se can actively promote sensitization-dependent eosinophil recruitment to the peritoneal cavity after a second exposure through the production of eosinophilotactic signals such as eotaxin"
Directly supports sensitization-dependent eosinophil recruitment through eotaxin on second exposure.
PMID:30258210 SUPPORT BACKGROUND Human Clinical
"This condition can be life threatening when the allergic reaction is triggered systemically progressing to anaphylactic shock"
Supports progression of the systemic form of this reaction to anaphylactic shock.
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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Fire Ant Poisoning Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

13
Cardiovascular 3
Erythema HP:0010783 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Erythema (HP:0010783). HP:0010783 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"accompanied by redness and the development of raised wheals and white pustules at the sting site"
Supports erythema at the sting site as part of the typical local reaction.
Urticaria FREQUENT HP:0001025 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Urticaria (HP:0001025). HP:0001025 is a phenotype from the Human Phenotype Ontology.
Deliberately not scoped to a subtype. The reported category spans local urticarial change after an ordinary sting and generalized urticaria as part of a systemic reaction, and the source does not separate them.
Show evidence (2 references)
PMID:42302087 SUPPORT Human Clinical
"2,916 (33.33%) presented with urticaria or papules"
Quantitative basis for the FREQUENT band: urticaria or papules were recorded in 33.33% of cases, within the 30-79% range.
PMID:42302087 SUPPORT Human Clinical
"followed by IgE-mediated urticarial and erythematous reactions"
Supports the urticarial component as IgE-mediated rather than part of the direct alkaloid injury.
Lymphadenopathy HP:0002716 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Lymphadenopathy (HP:0002716). HP:0002716 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"82 (0.94%) exhibited localized allergic lymphadenopathy"
Supports localized allergic lymphadenopathy as a reported manifestation, at a frequency below 1%.
Immune 3
Pustule FREQUENT HP:0200039 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pustule (HP:0200039). HP:0200039 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:42302087 SUPPORT Human Clinical
"3,160 (36.12%) developed vesicles or pustules"
Quantitative basis for the FREQUENT band: vesicles or pustules were recorded in 36.12% of cases, within the 30-79% range.
PMID:28873251 SUPPORT Human Clinical
"A subepidermal pustule was noted in half of the cases."
Independent histopathologic support for the pustule, in a biopsied series rather than a symptom compilation.
Venom-induced anaphylaxis HP:0500096 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Venom-induced anaphylaxis (HP:0500096). HP:0500096 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:40230786 SUPPORT Human Clinical
"Fire ant and flying Hymenoptera-venom anaphylaxis prevalence in the general population was 0.048% and 0.083%, respectively."
Supports fire ant venom anaphylaxis as a measured clinical entity with a population prevalence.
PMID:37624246 SUPPORT REVIEW SYNTHESIS Other
"Systemic allergic reactions to fire ant stings are observed in approximately 2% of victims"
Independent estimate of the proportion of stung people who react systemically, quoted here because it differs from the other reported figures.
Anaphylactic shock VERY_RARE HP:0100845 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Anaphylactic shock (HP:0100845). HP:0100845 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"173 (1.98%) experienced dizziness or headache, 102 (1.17%) suffered shock"
Quantitative basis for the VERY_RARE band: shock was recorded in 1.17% of cases, within the 1-4% range.
Integument 3
Pruritus FREQUENT HP:0000989 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pruritus (HP:0000989). HP:0000989 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"Among the 8,749 collected cases, 6,784 (77.54%) experienced itching and pain, 3,160 (36.12%) developed vesicles or pustules, and 2,916 (33.33%) presented with urticaria or papules."
Quantitative basis for the FREQUENT band: itching and pain were recorded in 77.54% of cases, within the 30-79% range.
Skin vesicle HP:0200037 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Skin vesicle (HP:0200037). HP:0200037 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"3,160 (36.12%) developed vesicles or pustules"
Supports vesicles as a reported lesion, recorded in a combined category with pustules.
Papule HP:0200034 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Papule (HP:0200034). HP:0200034 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"2,916 (33.33%) presented with urticaria or papules"
Supports papules as a reported lesion, recorded in a combined category with urticaria.
Metabolism 2
Laryngeal edema HP:0012027 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Laryngeal edema (HP:0012027). HP:0012027 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"potentially leading to laryngeal edema, asthma, respiratory distress, or even anaphylactic shock"
Supports laryngeal edema as a documented manifestation of the systemic allergic reaction.
Fever VERY_RARE HP:0001945 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Fever (HP:0001945). HP:0001945 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"658 cases (7.52%) developed systemic allergy, 232 (2.65%) had fever"
Quantitative basis for the VERY_RARE band: fever was recorded in 2.65% of cases, within the 1-4% range.
Nervous System 1
Headache VERY_RARE HP:0002315 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Headache (HP:0002315). HP:0002315 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"173 (1.98%) experienced dizziness or headache"
Quantitative basis for the VERY_RARE band: the combined dizziness-or-headache category was recorded in 1.98% of cases.
Constitutional 1
Pain FREQUENT HP:0012531 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Pain (HP:0012531). HP:0012531 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:42302087 SUPPORT Human Clinical
"The typical local reactions following RIFA stings are itching and burning pain"
Supports burning pain as a typical immediate local reaction.
PMID:42302087 SUPPORT Human Clinical
"Among the 8,749 collected cases, 6,784 (77.54%) experienced itching and pain"
Quantitative basis for the FREQUENT band: the combined itching-and-pain category was recorded in 77.54% of cases.
💊

Medical Actions

3
Epinephrine for systemic reactions
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Agent: epinephrine CHEBI:33568 Chemical Entities of Biological Interest (CHEBI) Relation: this treatment uses this therapeutic agent This treatment uses epinephrine, annotated with adrenaline (CHEBI:33568). CHEBI:33568 is a therapeutic agent from Chemical Entities of Biological Interest.
Platform: Small molecule
Epinephrine is the first-line treatment for a systemic reaction, and prompt administration is the intervention that prevents death. Underuse is a documented problem: fire ant venom anaphylaxis in systemic mastocytosis is frequently misdiagnosed and not treated with epinephrine.
Mechanism Target:
MODULATES IgE-mediated mast cell activation on re-exposure — Epinephrine opposes the physiological consequences of mediator release rather than preventing degranulation, reversing vasodilation, capillary leak and bronchoconstriction.
Show evidence (1 reference)
PMID:40230786 SUPPORT INDIRECT Human Clinical
"Fire ant-venom anaphylaxis in systemic mastocytosis is frequently misdiagnosed and not treated with epinephrine."
Graded INDIRECT because the source establishes epinephrine as the expected treatment for this reaction by reporting its omission as a deficiency, rather than measuring its effect on the mast cell mediator mechanism.
Show evidence (1 reference)
PMID:40230786 SUPPORT Human Clinical
"Fire ant-venom anaphylaxis in systemic mastocytosis is frequently misdiagnosed and not treated with epinephrine."
Supports both the expected role of epinephrine and the documented failure to give it in the highest-risk group.
Fire ant whole-body extract venom immunotherapy
Action: fire ant whole-body extract immunotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is fire ant whole-body extract immunotherapy, annotated with Immunotherapy (NCIT:C15262). NCIT:C15262 is a clinical intervention from the NCI Thesaurus. Ontology label: Immunotherapy NCIT:C15262
Platform: Other
Whole-body extract immunotherapy is the only disease-modifying treatment for fire ant venom allergy. In a multisite retrospective review, 85.7% of patients who had previously had a systemic reaction and who reached maintenance had no worse than a large local swelling after a subsequent sting, while only 2.9% had a systemic reaction to the immunotherapy itself.
Mechanism Target:
MODULATES Mast cell arming by venom-specific IgE — Immunotherapy changes the immune response to the venom allergens so that re-exposure produces a much attenuated reaction.
Show evidence (1 reference)
PMID:37781270 SUPPORT Human Clinical
"Imported fire ant (IFA) venom immunotherapy (VIT) is the only disease-modifying treatment reported to be effective at decreasing the risk of systemic reactions (SRs) to IFA stings."
Supports immunotherapy acting on the sensitized state itself, which is what makes it disease-modifying rather than symptomatic.
Show evidence (3 references)
PMID:37781270 SUPPORT Human Clinical
"A substantial proportion of patients undergoing IFA VIT experienced protection against anaphylaxis with reexposure, with relatively few adverse events."
Supports both efficacy against anaphylaxis on re-exposure and an acceptable adverse-event rate.
PMID:37781270 SUPPORT Human Clinical
"85.7% (24 of 28) of the subjects noted symptoms no worse than a large swelling reaction after a repeat IFA sting. Notably, only 2.9% of the subjects (4 of 137) had an SR due to VIT."
Quantifies both the protective effect on re-sting and the rate of systemic reactions caused by the treatment itself.
PMID:40230786 SUPPORT Human Clinical
"whole-body extract IT (WBE-IT) is effective in the treatment of FA-venom anaphylaxis"
Independent support for whole-body extract immunotherapy as effective treatment for the anaphylactic form.
Avoidance of occupied mounds and repeated stings
Action: fire ant exposure avoidanceNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is fire ant exposure avoidance, annotated with Lifestyle Therapy (NCIT:C15900). NCIT:C15900 is a clinical intervention from the NCI Thesaurus. Ontology label: Lifestyle Therapy NCIT:C15900
Platform: Behavioral / lifestyle
Because the venom is already injected by the time the disease begins, prevention is exposure reduction: avoiding occupied nests, and for a person with a previous systemic reaction, carrying prescribed epinephrine.
Mechanism Target:
INHIBITS Fire ant sting and venom deposition in skin — Avoiding contact prevents the venom deposition that initiates the disease.
Show evidence (1 reference)
PMID:37355195 SUPPORT INDIRECT Human Clinical
"Fire ants display a behavioral adaptation to survive flooding, called "rafting," bringing humans into even more contact with fire ants."
Graded INDIRECT because the source identifies contact as the modifiable step and names a circumstance that increases it, rather than measuring the effect of an avoidance intervention.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"There is an urgent need for enhanced protective measures and treatment options."
Supports protective measures as a recognized need in affected regions.
🌍

Environmental Factors

2
Fire ant sting on nest disturbance
exposure to Solenopsis venom by fire ant sting ECTO:0000537 Environmental Conditions, Treatments and Exposures Ontology (ECTO) Relation: this environmental factor is this exposure This environmental factor is exposure to Solenopsis venom by fire ant sting, annotated with exposure to toxin (ECTO:0000537), qualified as has input solenopsin A. ECTO:0000537 is an exposure from the Environmental Conditions, Treatments and Exposures Ontology.
No ECTO class binds this exposure precisely. Searched the local ECTO build on 2026-10-06 with `runoak -i sqlite:obo:ecto info` for `l~venom`, `l~sting`, `l~bite`, `l~arthropod`, `l~insect`, `l~envenom`, `l~hymenoptera` and `l~animal`. The first six return no ECTO term at all; `l~insect` returns only insecticide-exposure classes such as ECTO:9000089; `l~animal` returns only animal-waste and manure classes. ECTO:0000537 exposure to toxin is therefore bound as the nearest true parent, with the specificity carried in `preferred_term` and the venom alkaloid attached as a qualifier. This follows the convention already used by the sibling envenomation entries Scorpion_Envenomation and Black_Widow_Spider_Envenomation, which bind ECTO:0000537 and ECTO:0000730 the same way.
The ordinary route of exposure is disturbing an occupied mound, after which workers swarm and sting repeatedly. Risk follows ant distribution, nest density and human contact, so outdoor work, agriculture and infested green space matter more than any host factor.
Show evidence (2 references)
PMID:42302087 SUPPORT Human Clinical
"When a RIFA nest is disturbed, the workers rapidly swarm out to attack the intruder using their stings and venom"
Supports nest disturbance followed by swarming attack as the ordinary exposure route.
PMID:37355195 SUPPORT Human Clinical
"Imported fire ants aggressively sting humans, leading to a variety of local and systemic effects."
Supports aggressive stinging of humans as the exposure event behind both local and systemic disease.
Mechanism Target:
TRIGGERS Fire ant sting and venom deposition in skin — The sting is the physical act that deposits venom in the skin.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"When a RIFA nest is disturbed, the workers rapidly swarm out to attack the intruder using their stings and venom"
Supports the exposure initiating the venom deposition step of the mechanism.
🔬

Diagnosis

3
Venom sensitization testing after a systemic reaction
After a systemic reaction, sensitization is confirmed by skin testing with whole-body extract or by serum venom-specific IgE. In a mastocytosis cohort, 13 of 14 patients with a clinical history of fire ant venom anaphylaxis had evidence of sensitization by one or the other. The test confirms sensitization rather than predicting who will react, since sensitization rates in colonized regions far exceed the anaphylaxis prevalence.
venom skin testing NCIT:C17137 NCI Thesaurus (NCIT)
Show evidence (2 references)
PMID:40230786 SUPPORT Human Clinical
"Thirteen of 14 patients with a clinical history of FA-venom anaphylaxis had evidence of sensitization by skin testing or serum specific-IgE testing."
Supports skin testing and serum specific-IgE as the confirmatory tests, with their yield in a clinically characterized cohort.
PMID:37781270 SUPPORT Human Clinical
"The in vitro IFA sensitization rates in our prospective cohort ranged from 19.1% to 24.1%."
Quantifies in vitro sensitization rates, which is the background against which a positive result has to be interpreted.
Serum venom-specific IgE measurement
Serum fire ant specific IgE is measured alongside total IgE and tryptase. A positive result establishes sensitization; total IgE is measured so that a high background level is not mistaken for specific sensitization.
venom-specific immunoglobulin E measurement NCIT:C81970 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:37781270 SUPPORT Human Clinical
"Serum was tested for IFA IgE via ICAP as well as by measuring tryptase and total IgE levels"
Supports the specific-IgE assay performed together with tryptase and total IgE.
Basal serum tryptase for mastocytosis screening
Because systemic mastocytosis is a major risk factor for severe venom anaphylaxis, a patient with a systemic reaction is screened for it by examination for cutaneous mastocytosis lesions and by a basal serum tryptase-based risk score. Nearly half of fire ant venom anaphylaxis episodes in that cohort were not initially recognized as anaphylaxis at all, which is the practical reason this screening matters.
basal serum tryptase measurement NCIT:C92292 NCI Thesaurus (NCIT)
Show evidence (2 references)
PMID:40230786 SUPPORT Human Clinical
"Patients with FH anaphylaxis are screened for SM by a) physical exam to identify monomorphic lesions of maculopapular cutaneous mastocytosis, b) calculation of a symptom- and basal serum tryptase (BST)-based risk scoring tool"
Supports the stated screening pathway for systemic mastocytosis after venom anaphylaxis.
PMID:40230786 SUPPORT Human Clinical
"Nearly half of all episodes of FA-venom anaphylaxis were not initially diagnosed as anaphylaxis or treated with epinephrine"
Supports under-recognition of the reaction itself, which is what makes systematic screening after an episode necessary.
📈

Progression

5
Immediate local reaction
Burning pain, itching, erythema and a wheal appear immediately on stinging, driven by the alkaloid fraction rather than by any immune memory.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"The typical local reactions following RIFA stings are itching and burning pain, accompanied by redness and the development of raised wheals and white pustules at the sting site"
Supports the immediate local phase of pain, itching, erythema and wheal formation.
Pustule formation over 48 hours
The lesion evolves through a distinctive histopathologic sequence, with a sterile subepidermal pustule forming over a wedge-shaped area of degenerated dermal collagen.
Show evidence (1 reference)
PMID:28873251 SUPPORT Human Clinical
"The typical lesion follows a very distinctive clinical and histopathologic evolution over 48 hours, with the formation of a subepidermal pustule overlying a wedge-shaped area of dermal collagen basophilic degeneration with scattered neutrophils."
Supports a defined 48-hour evolution to the characteristic subepidermal pustule, documented by prospective biopsy.
Sensitization between exposures
Between a first and a later sting, venom proteins drive antigen presentation and class switching to venom-specific IgE. In the mouse model, challenge fourteen days after sensitization produced the allergic response; the corresponding interval in an individual human is not fixed.
Show evidence (1 reference)
PMID:30258210 SUPPORT PRIMARY RESULT Model Organism
"Following sensitization and a second exposure, a marked footpad swelling was observed."
Supports a latent sensitization interval between exposures, after which a second exposure produces an amplified response.
Systemic reaction on re-exposure
In a sensitized person a subsequent sting can produce a systemic reaction within minutes, and repeated exposure can make successive reactions more severe.
Show evidence (1 reference)
PMID:42302087 SUPPORT Human Clinical
"Repeated exposure to the allergen can lead to progressively more severe allergic reactions"
Supports escalation of reaction severity across repeated exposures rather than a fixed per-sting risk.
Fatal outcome in a small minority
Death was recorded in 3 of 8,749 assembled cases (0.03%), and the reporting source attributes many fatalities to delayed or inadequate treatment rather than to the sting dose itself. That is the same pattern as the undertreatment of anaphylaxis with epinephrine documented in the mastocytosis cohort, which is why recognition rather than severity is the modifiable step.
Show evidence (2 references)
PMID:42302087 SUPPORT Human Clinical
"66 (0.75%) temporarily lost their voice (speech impediment), and 3 cases (0.03%) resulted in death"
Quantifies the fatal outcome within the assembled case series.
PMID:42302087 SUPPORT Human Clinical
"Previous studies have shown that many fatalities caused by RIFA stings result from delayed or inadequate treatment, leading to anaphylactic shock or secondary complications"
Supports delayed or inadequate treatment, rather than the envenomation alone, as the route to most reported deaths.
📊

Prevalence

2
United States Tricare beneficiaries, general population
Point Prevalence 48.0 per 100,000 1–9 per 10,000 Fire Ant Venom Anaphylaxis
0.048% (4.8 per 10,000) in a population of 2,835,948 beneficiaries enrolled in direct care, estimated by combining an immunotherapy prescription database with an ICD-10 registry corrected by a chart-review true-positive rate. More than 95% of the beneficiary population lived in the United States. This is the prevalence of the anaphylactic form, not of being stung.
Show evidence (1 reference)
PMID:40230786 SUPPORT Human Clinical
"Fire ant and flying Hymenoptera-venom anaphylaxis prevalence in the general population was 0.048% and 0.083%, respectively."
States the measured general-population prevalence of fire ant venom anaphylaxis.
United States, the 14 states colonized by fire ants
Point Prevalence 85.0 per 100,000 1–9 per 10,000 Fire Ant Venom Anaphylaxis
0.085% (8.5 per 10,000) when restricted to the fourteen states the ants have colonized, roughly double the all-states figure, which is the expected effect of restricting the denominator to where exposure actually occurs.
Show evidence (1 reference)
PMID:40230786 SUPPORT Human Clinical
"Fire ant-venom anaphylaxis prevalence in the 14 colonized states was 0.085%."
States the measured prevalence restricted to the colonized states.
🔀

Differential Diagnoses

1

Conditions with similar clinical presentations that must be differentiated from Fire Ant Poisoning:

Flying Hymenoptera venom anaphylaxis
Distinguishing Features
  • Both produce IgE-mediated venom anaphylaxis, so the systemic presentations overlap closely
  • The fire ant sting leaves a characteristic sterile pustule that flying Hymenoptera stings do not
  • Fire ants deliver far less venom protein per sting, 10 to 100 ng against 2 to 20 micrograms for vespids
  • Immunotherapy differs by preparation: fire ant allergy is treated with whole-body extract, flying Hymenoptera with venom extract
Show evidence (2 references)
PMID:40230786 SUPPORT Human Clinical
"The amount of venom protein delivered in a single sting is highest in honey bee (25-150 mcg) and vespids (2-20 mcg) and lowest in FAs (10-100 ng)"
Quantifies the venom protein dose difference that distinguishes fire ant from flying Hymenoptera envenomation.
PMID:28873251 SUPPORT Human Clinical
"Skin reactions to the sting of the imported fire ant have characteristic clinicopathological features."
Supports that the local fire ant lesion is distinctive enough to separate it from other arthropod stings.
{ }

Source YAML

click to show 
name: Fire Ant Poisoning
creation_date: "2026-10-06T21:33:56Z"
category: Injury
categories:
- Envenomation
- Toxic Exposure Disorder
- Allergic Disorder
synonyms:
- fire ant sting
- fire ant envenomation
- imported fire ant sting reaction
- red imported fire ant envenomation
- fire ant venom allergy
description: >-
  Fire ant poisoning is the acute injury produced when a Solenopsis worker ant
  anchors itself with its jaws and injects venom through an abdominal stinger,
  often repeatedly. Two mechanisms run in parallel from the same sting and
  account for the whole clinical range. The venom is overwhelmingly
  water-insoluble piperidine alkaloids, which are directly cytotoxic and produce
  immediate burning pain, a wheal, and the characteristic sterile pustule without
  any prior sensitization. A much smaller protein fraction carries the allergens
  Sol i 1 to Sol i 4, which drive IgE-mediated sensitization; on re-exposure a
  sensitized person can develop urticaria, airway compromise, or anaphylactic
  shock. The alkaloid branch is near-universal and self-limited; the protein
  branch is uncommon and is what kills.
disease_term:
  preferred_term: fire ant poisoning
  term:
    id: MONDO:0100341
    label: fire ant poisoning
mappings:
  mondo_mappings:
  - term:
      id: MONDO:0100341
      label: fire ant poisoning
    mapping_predicate: skos:exactMatch
    mapping_source: MONDO
    mapping_justification: Primary MONDO disease identifier for fire ant poisoning.
classifications:
  harrisons_chapter:
  - classification_value: POISONING_ENVENOMATION
    evidence:
    - reference: PMID:37355195
      reference_title: "Envenomation From Flood-Related Fire Ant Rafting: A Cautionary Note."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Imported fire ants aggressively sting humans, leading to a variety of local and systemic effects."
      explanation: Identifies the disorder as an envenomation injury with local and systemic effects, supporting the primary Harrison's home in Poisoning, Drug Overdose, and Envenomation.
  - classification_value: IMMUNE_RHEUMATOLOGIC
    evidence:
    - reference: PMID:30258210
      reference_title: "The allergic response mediated by fire ant venom proteins."
      supports: SUPPORT
      quote_role: PRIMARY_RESULT
      evidence_source: MODEL_ORGANISM
      snippet: "Based on eosinophil recruitment and production of Th2 cytokines, we hereby establish that fire ant proteins per se can lead to an allergic response"
      explanation: Supports a secondary immune classification because the life-threatening form of the disease is an IgE-mediated type 2 hypersensitivity reaction.
definitions:
- name: Clinical case definition for fire ant poisoning
  definition_type: CASE_DEFINITION
  description: >-
    Fire ant poisoning is an acute, exposure-dependent sting injury in which
    Solenopsis venom is injected into skin, producing immediate local alkaloid
    toxicity and, in a sensitized minority, an IgE-mediated systemic allergic
    reaction. It is not an inherited disorder and requires no host genotype.
  scope: Disease-level framing covering both the direct-toxicity and allergic routes
  evidence:
  - reference: PMID:30258210
    reference_title: "The allergic response mediated by fire ant venom proteins."
    supports: SUPPORT
    quote_role: BACKGROUND
    evidence_source: HUMAN_CLINICAL
    snippet: "Immediate effects of the stings are mainly caused by a major (>95%) fraction of toxic alkaloids, but the later allergic responses"
    explanation: Supports the two-mechanism definition by separating immediate alkaloid-driven effects from the later protein-driven allergic response.
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "When a RIFA nest is disturbed, the workers rapidly swarm out to attack the intruder using their stings and venom"
    explanation: Supports that the necessary cause is contact with and venom injection by a stinging fire ant.
- name: Practical diagnostic definition for fire ant sting reaction
  definition_type: DIAGNOSTIC_CRITERIA
  description: >-
    Diagnosis is clinical, from the exposure history plus the characteristic
    lesion evolution. Where a biopsy is taken, a superficial and deep neutrophilic
    infiltrate with basophilic collagen degeneration supports the diagnosis even
    when the sterile pustule is absent.
  scope: Clinical and histopathologic recognition of a fire ant sting reaction
  evidence:
  - reference: PMID:28873251
    reference_title: "Imported fire ant envenomation: A clinicopathologic study of a recognizable form of arthropod assault reaction."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Skin reactions to the sting of the imported fire ant have characteristic clinicopathological features."
    explanation: Supports that the sting reaction is clinically and histopathologically recognizable.
  - reference: PMID:28873251
    reference_title: "Imported fire ant envenomation: A clinicopathologic study of a recognizable form of arthropod assault reaction."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the main features were a superficial and deep dermal, perivascular, periadnexal and interstitial infiltrate consisting of neutrophils, with basophilic degeneration of the collagen"
    explanation: Supports the specific histopathologic pattern used to support the diagnosis.
parents:
- poisoning
has_subtypes:
- name: Local Sting Reaction
  display_name: Local sting reaction (direct alkaloid toxicity)
  description: >-
    The near-universal form. Piperidine alkaloids injected into skin are directly
    cytotoxic, producing immediate burning pain and itching, a wheal, and a
    characteristic sterile pustule over roughly 24 hours. No prior sensitization
    is required, and large local reactions can persist up to 72 hours.
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The typical local reactions following RIFA stings are itching and burning pain, accompanied by redness and the development of raised wheals and white pustules at the sting site, followed by IgE-mediated urticarial and erythematous reactions"
    explanation: Supports the local reaction as the typical presentation, and separates it from the subsequent IgE-mediated component.
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "56% of stung individuals experience noticeable localized reactions, whereas only 0.5-2% exhibit systemic allergy"
    explanation: Supports that localized reactions dominate numerically over systemic allergy by roughly two orders of magnitude.
- name: Fire Ant Venom Anaphylaxis
  display_name: Fire ant venom anaphylaxis (IgE-mediated systemic reaction)
  description: >-
    The uncommon but life-threatening form. In a person sensitized to the venom
    protein allergens, re-exposure triggers IgE-dependent mast cell activation,
    producing generalized urticaria, angioedema, airway compromise, or
    circulatory collapse. Systemic mastocytosis is a major risk factor, and in
    that group the reaction is frequently misdiagnosed and undertreated.
  evidence:
  - reference: PMID:40230786
    reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fire ant and flying Hymenoptera-venom anaphylaxis prevalence in the general population was 0.048% and 0.083%, respectively."
    explanation: Supports fire ant venom anaphylaxis as a measurable distinct clinical entity with its own population prevalence.
  - reference: PMID:40230786
    reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fire ant-venom anaphylaxis in systemic mastocytosis is frequently misdiagnosed and not treated with epinephrine."
    explanation: Supports that the systemic form is underrecognized and undertreated in the highest-risk host group.
prevalence:
- population: United States Tricare beneficiaries, general population
  measure_type: POINT_PREVALENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 48.0
  rate_denominator: POPULATION
  subtype: Fire Ant Venom Anaphylaxis
  notes: >-
    0.048% (4.8 per 10,000) in a population of 2,835,948 beneficiaries enrolled
    in direct care, estimated by combining an immunotherapy prescription database
    with an ICD-10 registry corrected by a chart-review true-positive rate. More
    than 95% of the beneficiary population lived in the United States. This is
    the prevalence of the anaphylactic form, not of being stung.
  evidence:
  - reference: PMID:40230786
    reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fire ant and flying Hymenoptera-venom anaphylaxis prevalence in the general population was 0.048% and 0.083%, respectively."
    explanation: States the measured general-population prevalence of fire ant venom anaphylaxis.
- population: United States, the 14 states colonized by fire ants
  measure_type: POINT_PREVALENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 85.0
  rate_denominator: POPULATION
  subtype: Fire Ant Venom Anaphylaxis
  notes: >-
    0.085% (8.5 per 10,000) when restricted to the fourteen states the ants have
    colonized, roughly double the all-states figure, which is the expected effect
    of restricting the denominator to where exposure actually occurs.
  evidence:
  - reference: PMID:40230786
    reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fire ant-venom anaphylaxis prevalence in the 14 colonized states was 0.085%."
    explanation: States the measured prevalence restricted to the colonized states.
progression:
- phase: Immediate local reaction
  notes: >-
    Burning pain, itching, erythema and a wheal appear immediately on stinging,
    driven by the alkaloid fraction rather than by any immune memory.
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The typical local reactions following RIFA stings are itching and burning pain, accompanied by redness and the development of raised wheals and white pustules at the sting site"
    explanation: Supports the immediate local phase of pain, itching, erythema and wheal formation.
- phase: Pustule formation over 48 hours
  notes: >-
    The lesion evolves through a distinctive histopathologic sequence, with a
    sterile subepidermal pustule forming over a wedge-shaped area of degenerated
    dermal collagen.
  evidence:
  - reference: PMID:28873251
    reference_title: "Imported fire ant envenomation: A clinicopathologic study of a recognizable form of arthropod assault reaction."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The typical lesion follows a very distinctive clinical and histopathologic evolution over 48 hours, with the formation of a subepidermal pustule overlying a wedge-shaped area of dermal collagen basophilic degeneration with scattered neutrophils."
    explanation: Supports a defined 48-hour evolution to the characteristic subepidermal pustule, documented by prospective biopsy.
- phase: Sensitization between exposures
  notes: >-
    Between a first and a later sting, venom proteins drive antigen presentation
    and class switching to venom-specific IgE. In the mouse model, challenge
    fourteen days after sensitization produced the allergic response; the
    corresponding interval in an individual human is not fixed.
  evidence:
  - reference: PMID:30258210
    reference_title: "The allergic response mediated by fire ant venom proteins."
    supports: SUPPORT
    quote_role: PRIMARY_RESULT
    evidence_source: MODEL_ORGANISM
    snippet: "Following sensitization and a second exposure, a marked footpad swelling was observed."
    explanation: Supports a latent sensitization interval between exposures, after which a second exposure produces an amplified response.
- phase: Systemic reaction on re-exposure
  notes: >-
    In a sensitized person a subsequent sting can produce a systemic reaction
    within minutes, and repeated exposure can make successive reactions more
    severe.
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Repeated exposure to the allergen can lead to progressively more severe allergic reactions"
    explanation: Supports escalation of reaction severity across repeated exposures rather than a fixed per-sting risk.
- phase: Fatal outcome in a small minority
  notes: >-
    Death was recorded in 3 of 8,749 assembled cases (0.03%), and the reporting
    source attributes many fatalities to delayed or inadequate treatment rather
    than to the sting dose itself. That is the same pattern as the undertreatment
    of anaphylaxis with epinephrine documented in the mastocytosis cohort, which
    is why recognition rather than severity is the modifiable step.
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "66 (0.75%) temporarily lost their voice (speech impediment), and 3 cases (0.03%) resulted in death"
    explanation: Quantifies the fatal outcome within the assembled case series.
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Previous studies have shown that many fatalities caused by RIFA stings result from delayed or inadequate treatment, leading to anaphylactic shock or secondary complications"
    explanation: Supports delayed or inadequate treatment, rather than the envenomation alone, as the route to most reported deaths.
pathophysiology:
- name: Fire ant sting and venom deposition in skin
  description: >-
    A worker ant anchors with its mandibles and injects venom through an
    abdominal stinger, usually several times. The injected volume is small, with
    only 10 to 100 ng of protein per sting, but the venom is overwhelmingly
    alkaloid by mass and both fractions are delivered together into the
    superficial skin.
  biological_scale: ORGANISM
  locations:
  - preferred_term: skin of body
    term:
      id: UBERON:0002097
      label: skin of body
  biological_processes:
  - preferred_term: response to toxic substance
    modifier: INCREASED
    term:
      id: GO:0009636
      label: response to toxic substance
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "When a RIFA nest is disturbed, the workers rapidly swarm out to attack the intruder using their stings and venom"
    explanation: Directly supports venom injection by swarming workers as the initiating event.
  - reference: PMID:37624246
    reference_title: "Chemistry and Functions of Imported Fire Ant Venom."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: "fire ant venoms are characterized by a high proportion of water-insoluble alkaloids and a small number of water-soluble proteins"
    explanation: Supports that the deposited venom is predominantly alkaloid with a minor protein fraction, which is what gives the disease its two branches.
  downstream:
  - target: Piperidine alkaloid cytotoxic injury to skin
    causal_link_type: DIRECT
    description: The dominant alkaloid fraction injures cells at the sting site directly.
    evidence:
    - reference: PMID:30258210
      reference_title: "The allergic response mediated by fire ant venom proteins."
      supports: SUPPORT
      quote_role: BACKGROUND
      evidence_source: HUMAN_CLINICAL
      snippet: "Immediate effects of the stings are mainly caused by a major (>95%) fraction of toxic alkaloids, but the later allergic responses"
      explanation: Supports that the immediate consequence of the sting is attributable to the alkaloid fraction.
  - target: Venom protein antigen presentation and type 2 sensitization
    causal_link_type: DIRECT
    description: In parallel, the minor protein fraction is taken up and processed by antigen-presenting cells.
    evidence:
    - reference: PMID:30258210
      reference_title: "The allergic response mediated by fire ant venom proteins."
      supports: SUPPORT
      evidence_source: IN_VITRO
      snippet: "This demonstrates that the venom proteins can directly activate dendritic cells to promote antigen presentation"
      explanation: Supports a second, parallel branch in which the venom proteins initiate antigen presentation.
- name: Piperidine alkaloid cytotoxic injury to skin
  description: >-
    The piperidine alkaloids, named solenopsins, make up over 95% of the venom
    and are directly cytotoxic. In vitro they killed dendritic cells at 10
    micrograms per millilitre, which is why the authors concluded the alkaloids
    are not the immunogenic component. This cytotoxicity is the basis of the
    immediate burning pain and local injury, and it requires no immune memory.
  biological_scale: CELLULAR
  locations:
  - preferred_term: skin epidermis
    term:
      id: UBERON:0001003
      label: skin epidermis
  cell_types:
  - preferred_term: keratinocyte
    term:
      id: CL:0000312
      label: keratinocyte
  chemical_entities:
  - preferred_term: solenopsin A
    term:
      id: CHEBI:80722
      label: (-)-Solenopsin A
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:30258210
    reference_title: "The allergic response mediated by fire ant venom proteins."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: "The venom alkaloids proved extremely cytotoxic even at 10"
    explanation: Directly supports marked cytotoxicity of the venom alkaloid fraction in cell culture.
  - reference: PMID:37624246
    reference_title: "Chemistry and Functions of Imported Fire Ant Venom."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: "These piperidine alkaloids were commonly named solenopsins"
    explanation: Establishes the identity of the alkaloid class responsible for the direct toxicity.
  notes: >-
    The cytotoxicity figure is from cultured murine bone-marrow-derived dendritic
    cells, not from human skin. The precise molecular target in human sting
    lesions is not established, and no Wnt, MAPK or mTOR signalling lesion is
    asserted: isolated-solenopsin data from cancer-cell models do not transfer
    to clinical envenomation.
  downstream:
  - target: Neutrophilic dermal infiltration and collagen degeneration
    causal_link_type: DIRECT
    description: Local cytotoxic injury recruits a dense neutrophilic infiltrate and degenerates dermal collagen.
    evidence:
    - reference: PMID:28873251
      reference_title: "Imported fire ant envenomation: A clinicopathologic study of a recognizable form of arthropod assault reaction."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "the main features were a superficial and deep dermal, perivascular, periadnexal and interstitial infiltrate consisting of neutrophils, with basophilic degeneration of the collagen"
      explanation: Human biopsy evidence for the neutrophilic infiltrate and collagen degeneration that follow the local injury.
  - target: Pruritus
    causal_link_type: DIRECT
    description: Local alkaloid injury produces the immediate itching that is the most frequently reported symptom.
    evidence:
    - reference: PMID:42302087
      reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The typical local reactions following RIFA stings are itching and burning pain, accompanied by redness and the development of raised wheals and white pustules at the sting site"
      explanation: Supports itching as a direct and immediate local consequence of the sting.
  - target: Pain
    causal_link_type: DIRECT
    description: The same local alkaloid injury produces immediate burning pain.
    evidence:
    - reference: PMID:42302087
      reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The typical local reactions following RIFA stings are itching and burning pain"
      explanation: Supports burning pain as a direct and immediate local consequence of the sting.
  - target: Erythema
    causal_link_type: DIRECT
    description: Local injury and the accompanying inflammatory response produce redness at the sting site.
    evidence:
    - reference: PMID:42302087
      reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "accompanied by redness and the development of raised wheals and white pustules at the sting site"
      explanation: Supports erythema at the sting site as part of the immediate local reaction.
- name: Neutrophilic dermal infiltration and collagen degeneration
  description: >-
    Biopsies taken in a clinical setting show a superficial and deep dermal
    infiltrate of neutrophils in perivascular, periadnexal and interstitial
    distribution, accompanied by basophilic degeneration of dermal collagen. This
    pattern is itself diagnostically useful even when the pustule is absent.
  biological_scale: TISSUE
  locations:
  - preferred_term: dermis
    term:
      id: UBERON:0002067
      label: dermis
  cell_types:
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  biological_processes:
  - preferred_term: inflammatory response
    modifier: INCREASED
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:28873251
    reference_title: "Imported fire ant envenomation: A clinicopathologic study of a recognizable form of arthropod assault reaction."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the main features were a superficial and deep dermal, perivascular, periadnexal and interstitial infiltrate consisting of neutrophils, with basophilic degeneration of the collagen"
    explanation: Directly supports the neutrophilic infiltrate and collagen degeneration as the tissue-level lesion.
  downstream:
  - target: Sterile subepidermal pustule formation
    causal_link_type: DIRECT
    description: The neutrophilic infiltrate organizes into a subepidermal pustule over about 48 hours.
    evidence:
    - reference: PMID:28873251
      reference_title: "Imported fire ant envenomation: A clinicopathologic study of a recognizable form of arthropod assault reaction."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "The typical lesion follows a very distinctive clinical and histopathologic evolution over 48 hours, with the formation of a subepidermal pustule overlying a wedge-shaped area of dermal collagen basophilic degeneration with scattered neutrophils."
      explanation: Supports the step from neutrophilic infiltration and collagen degeneration to a subepidermal pustule, with the stated time course.
- name: Sterile subepidermal pustule formation
  description: >-
    The characteristic lesion is a sterile subepidermal pustule sitting over a
    wedge-shaped zone of degenerated dermal collagen. It was present in half of
    the retrospectively reviewed biopsies, so its absence does not exclude the
    diagnosis.
  biological_scale: TISSUE
  locations:
  - preferred_term: skin epidermis
    term:
      id: UBERON:0001003
      label: skin epidermis
  cell_types:
  - preferred_term: neutrophil
    term:
      id: CL:0000775
      label: neutrophil
  evidence:
  - reference: PMID:28873251
    reference_title: "Imported fire ant envenomation: A clinicopathologic study of a recognizable form of arthropod assault reaction."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A subepidermal pustule was noted in half of the cases."
    explanation: Supports the pustule as a characteristic but not invariable finding on biopsy.
  downstream:
  - target: Pustule
    causal_link_type: DIRECT
    description: The lesion presents clinically as the white pustule characteristic of a fire ant sting.
    evidence:
    - reference: PMID:42302087
      reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "the development of raised wheals and white pustules at the sting site"
      explanation: Supports the clinically visible white pustule as the manifestation of the histologic lesion.
  - target: Skin vesicle
    causal_link_type: DIRECT
    description: Earlier or less developed lesions are recorded clinically as vesicles.
    evidence:
    - reference: PMID:42302087
      reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "3,160 (36.12%) developed vesicles or pustules"
      explanation: Supports vesicles being recorded alongside pustules as the same reported lesion category.
- name: Venom protein antigen presentation and type 2 sensitization
  description: >-
    The minor water-soluble protein fraction carries the allergens Sol i 1 to
    Sol i 4. These proteins directly activate dendritic cells, upregulating MHC
    class II and the costimulatory molecule CD86, which licenses antigen
    presentation to naive T cells and a type 2 helper response with IL-4
    production. The venom proteins did this without any added adjuvant, and
    themselves acted as an adjuvant for an unrelated antigen.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: dendritic cell
    term:
      id: CL:0000451
      label: dendritic cell
  - preferred_term: T-helper 2 cell
    term:
      id: CL:0000546
      label: T-helper 2 cell
  biological_processes:
  - preferred_term: antigen processing and presentation of exogenous peptide antigen via MHC class II
    modifier: INCREASED
    term:
      id: GO:0019886
      label: antigen processing and presentation of exogenous peptide antigen via MHC class II
  - preferred_term: type 2 immune response
    modifier: INCREASED
    term:
      id: GO:0042092
      label: type 2 immune response
  evidence:
  - reference: PMID:30258210
    reference_title: "The allergic response mediated by fire ant venom proteins."
    supports: SUPPORT
    quote_role: PRIMARY_RESULT
    evidence_source: IN_VITRO
    snippet: "the venom proteins elicited an activation response, as shown by the upregulation of MHCII and CD86"
    explanation: Directly supports dendritic cell activation by venom proteins, measured as MHC class II and CD86 upregulation.
  - reference: PMID:30258210
    reference_title: "The allergic response mediated by fire ant venom proteins."
    supports: SUPPORT
    quote_role: PRIMARY_RESULT
    evidence_source: MODEL_ORGANISM
    snippet: "Based on eosinophil recruitment and production of Th2 cytokines, we hereby establish that fire ant proteins per se can lead to an allergic response"
    explanation: Supports that the venom proteins alone are sufficient to drive a type 2 allergic response.
  - reference: PMID:37624246
    reference_title: "Chemistry and Functions of Imported Fire Ant Venom."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: "four worker allergens have been isolated and characterized: Sol i 1, Sol i 2, Sol i 3, and Sol i 4"
    explanation: Establishes the identity of the four characterized venom protein allergens driving sensitization.
  downstream:
  - target: Venom-specific IgE class switching
    causal_link_type: DIRECT
    description: The type 2 response drives B cell class switching to venom-specific IgE.
    evidence:
    - reference: PMID:30258210
      reference_title: "The allergic response mediated by fire ant venom proteins."
      supports: SUPPORT
      directness: INDIRECT
      evidence_source: MODEL_ORGANISM
      snippet: "activated B cells mature into IgE-secretory plasma cells, and the secreted allergen-specific IgE bind to peripheral mast-cells"
      explanation: >-
        Names the IgE class-switching and mast-cell-binding step this edge
        asserts. Graded INDIRECT because the sentence is from the figure legend
        describing the authors' hypothesized scheme for the fire ant response
        rather than a measurement they report; the study did not quantify
        venom-specific IgE.
    - reference: PMID:30258210
      reference_title: "The allergic response mediated by fire ant venom proteins."
      supports: SUPPORT
      quote_role: BACKGROUND
      directness: INDIRECT
      evidence_source: OTHER
      snippet: "Once activated, Th2 lymphocytes will undergo clonal expansion leading to lymph node hyperplasia and production of IL-4"
      explanation: >-
        Background statement of general type 2 immunology, carried as context for
        the IL-4-driven response preceding class switching. Graded INDIRECT
        because the sentence does not mention IgE, so it supports the edge only
        through the established link from IL-4 to class switching.
- name: Venom-specific IgE class switching
  description: >-
    Activated B cells undergo clonal expansion and mature into IgE-secreting
    plasma cells producing antibody specific for the venom allergens. The
    sensitization rate to fire ant venom exceeds 90% in colonized regions, far
    above sensitization to other stinging Hymenoptera, so this state is common
    while anaphylaxis remains uncommon.
  biological_scale: MOLECULAR
  cell_types:
  - preferred_term: B cell
    term:
      id: CL:0000236
      label: B cell
  biological_processes:
  - preferred_term: immunoglobulin production
    modifier: INCREASED
    term:
      id: GO:0002377
      label: immunoglobulin production
  evidence:
  - reference: PMID:40230786
    reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the sensitization rate to FA venom can be >90% in colonized regions and is higher than sensitization to other stinging Hymenoptera"
    explanation: Supports that venom sensitization is near-universal in colonized regions, which is what makes the gap between sensitization and clinical anaphylaxis important.
  notes: >-
    Sensitization and disease are not the same thing here, and the gap is large:
    over 90% sensitization in colonized regions against a measured anaphylaxis
    prevalence of 0.085% in those states. A positive venom IgE test therefore does
    not identify who will react.
  downstream:
  - target: Mast cell arming by venom-specific IgE
    causal_link_type: DIRECT
    description: Secreted allergen-specific IgE binds the high-affinity receptor on peripheral mast cells.
    evidence:
    - reference: PMID:30258210
      reference_title: "The allergic response mediated by fire ant venom proteins."
      supports: SUPPORT
      directness: INDIRECT
      evidence_source: MODEL_ORGANISM
      snippet: "activated B cells mature into IgE-secretory plasma cells, and the secreted allergen-specific IgE bind to peripheral mast-cells"
      explanation: >-
        States the binding of secreted allergen-specific IgE to peripheral mast
        cells. Graded INDIRECT because the sentence is the authors' hypothesized
        scheme in a figure legend rather than a measurement they report.
- name: Mast cell arming by venom-specific IgE
  description: >-
    Venom-specific IgE occupies the high-affinity receptor on peripheral mast
    cells. This is the state that converts a subsequent ordinary sting into a
    potentially fatal event, and it is what whole-body extract immunotherapy
    acts on.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: mast cell
    term:
      id: CL:0000097
      label: mast cell
  evidence:
  - reference: PMID:30258210
    reference_title: "The allergic response mediated by fire ant venom proteins."
    supports: SUPPORT
    directness: INDIRECT
    evidence_source: MODEL_ORGANISM
    snippet: "activated B cells mature into IgE-secretory plasma cells, and the secreted allergen-specific IgE bind to peripheral mast-cells"
    explanation: >-
      States that secreted allergen-specific IgE binds peripheral mast cells,
      which is this node. Graded INDIRECT because it is the authors' hypothesized
      scheme rather than a reported measurement.
  downstream:
  - target: IgE-mediated mast cell activation on re-exposure
    causal_link_type: DIRECT
    description: Armed mast cells are primed to degranulate when venom antigen is encountered again.
    evidence:
    - reference: PMID:30258210
      reference_title: "The allergic response mediated by fire ant venom proteins."
      supports: SUPPORT
      quote_role: BACKGROUND
      evidence_source: HUMAN_CLINICAL
      snippet: "A second exposure to venom antigens triggers a stereotypical allergic response marked by acute vascular permeability and later eosinophil recruitment at the site of the sting."
      explanation: Supports the step from a sensitized state to an amplified stereotyped response on second exposure.
- name: IgE-mediated mast cell activation on re-exposure
  description: >-
    On a later sting, venom antigen cross-links IgE on armed mast cells and
    basophils, releasing mediators that produce acute vascular permeability,
    generalized urticaria and, when the reaction is systemic, airway obstruction
    or circulatory collapse. Eosinophil recruitment driven by eotaxin follows at
    the sting site.
  biological_scale: CELLULAR
  cell_types:
  - preferred_term: mast cell
    term:
      id: CL:0000097
      label: mast cell
  - preferred_term: eosinophil
    term:
      id: CL:0000771
      label: eosinophil
  biological_processes:
  - preferred_term: mast cell activation
    modifier: INCREASED
    term:
      id: GO:0045576
      label: mast cell activation
  - preferred_term: eosinophil chemotaxis
    modifier: INCREASED
    term:
      id: GO:0048245
      label: eosinophil chemotaxis
  evidence:
  - reference: PMID:30258210
    reference_title: "The allergic response mediated by fire ant venom proteins."
    supports: SUPPORT
    quote_role: PRIMARY_RESULT
    evidence_source: MODEL_ORGANISM
    snippet: "venom proteins per se can actively promote sensitization-dependent eosinophil recruitment to the peritoneal cavity after a second exposure through the production of eosinophilotactic signals such as eotaxin"
    explanation: Directly supports sensitization-dependent eosinophil recruitment through eotaxin on second exposure.
  - reference: PMID:30258210
    reference_title: "The allergic response mediated by fire ant venom proteins."
    supports: SUPPORT
    quote_role: BACKGROUND
    evidence_source: HUMAN_CLINICAL
    snippet: "This condition can be life threatening when the allergic reaction is triggered systemically progressing to anaphylactic shock"
    explanation: Supports progression of the systemic form of this reaction to anaphylactic shock.
  notes: >-
    The mediator-release step itself was explicitly not measured in the mouse
    study, whose authors mark it as part of their hypothesized scheme. The human
    evidence for this node is the observed clinical syndrome and its response to
    epinephrine and to venom immunotherapy, not a direct measurement of mast cell
    degranulation after a fire ant sting.
  downstream:
  - target: Urticaria
    causal_link_type: DIRECT
    description: Mediator release produces generalized itching, rash and wheals beyond the sting site.
    evidence:
    - reference: PMID:42302087
      reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Systemic allergic symptoms manifest as generalized itching, rashes, flushing, and swelling of the head, neck, and face, which may progress to the limbs and trunk, potentially leading to laryngeal edema, asthma, respiratory distress, or even anaphylactic shock"
      explanation: Supports generalized cutaneous manifestations as the consequence of a systemic allergic reaction.
  - target: Venom-induced anaphylaxis
    causal_link_type: DIRECT
    description: A systemic mediator release presents as venom-induced anaphylaxis.
    evidence:
    - reference: PMID:30258210
      reference_title: "The allergic response mediated by fire ant venom proteins."
      supports: SUPPORT
      quote_role: BACKGROUND
      evidence_source: HUMAN_CLINICAL
      snippet: "This condition can be life threatening when the allergic reaction is triggered systemically progressing to anaphylactic shock"
      explanation: Supports the step from a systemically triggered allergic reaction to life-threatening anaphylaxis.
  - target: Laryngeal edema
    causal_link_type: DIRECT
    description: Mediator-driven swelling of the upper airway threatens obstruction.
    evidence:
    - reference: PMID:42302087
      reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "potentially leading to laryngeal edema, asthma, respiratory distress, or even anaphylactic shock"
      explanation: Supports laryngeal edema as a documented consequence of the systemic reaction.
  - target: Anaphylactic shock
    causal_link_type: DIRECT
    description: Severe systemic mediator release causes circulatory collapse.
    evidence:
    - reference: PMID:42302087
      reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "potentially leading to laryngeal edema, asthma, respiratory distress, or even anaphylactic shock"
      explanation: Supports anaphylactic shock as the most severe consequence of the systemic reaction.
phenotypes:
- name: Pruritus
  category: Dermatologic
  subtype: Local Sting Reaction
  frequency: FREQUENT
  description: >-
    Itching, recorded together with pain, was the most frequently reported
    manifestation, in 77.54% of 8,749 assembled cases. It is immediate and does
    not require prior sensitization.
  phenotype_term:
    preferred_term: Pruritus
    term:
      id: HP:0000989
      label: Pruritus
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among the 8,749 collected cases, 6,784 (77.54%) experienced itching and pain, 3,160 (36.12%) developed vesicles or pustules, and 2,916 (33.33%) presented with urticaria or papules."
    explanation: "Quantitative basis for the FREQUENT band: itching and pain were recorded in 77.54% of cases, within the 30-79% range."
- name: Pain
  category: Dermatologic
  subtype: Local Sting Reaction
  frequency: FREQUENT
  description: >-
    Immediate burning pain at the sting site, recorded together with itching in
    77.54% of assembled cases.
  phenotype_term:
    preferred_term: Pain
    term:
      id: HP:0012531
      label: Pain
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The typical local reactions following RIFA stings are itching and burning pain"
    explanation: Supports burning pain as a typical immediate local reaction.
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Among the 8,749 collected cases, 6,784 (77.54%) experienced itching and pain"
    explanation: "Quantitative basis for the FREQUENT band: the combined itching-and-pain category was recorded in 77.54% of cases."
- name: Pustule
  category: Dermatologic
  subtype: Local Sting Reaction
  frequency: FREQUENT
  description: >-
    The characteristic sterile white pustule develops at the sting site over
    roughly a day. Vesicles or pustules were recorded in 36.12% of assembled
    cases.
  phenotype_term:
    preferred_term: Pustule
    term:
      id: HP:0200039
      label: Pustule
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "3,160 (36.12%) developed vesicles or pustules"
    explanation: "Quantitative basis for the FREQUENT band: vesicles or pustules were recorded in 36.12% of cases, within the 30-79% range."
  - reference: PMID:28873251
    reference_title: "Imported fire ant envenomation: A clinicopathologic study of a recognizable form of arthropod assault reaction."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A subepidermal pustule was noted in half of the cases."
    explanation: Independent histopathologic support for the pustule, in a biopsied series rather than a symptom compilation.
- name: Skin vesicle
  category: Dermatologic
  subtype: Local Sting Reaction
  description: >-
    Vesicles are recorded in the same reported category as pustules and likely
    represent an earlier or less developed stage of the same lesion. The source
    does not separate the two, so no independent frequency is given.
  phenotype_term:
    preferred_term: Skin vesicle
    term:
      id: HP:0200037
      label: Skin vesicle
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "3,160 (36.12%) developed vesicles or pustules"
    explanation: Supports vesicles as a reported lesion, recorded in a combined category with pustules.
- name: Erythema
  category: Dermatologic
  subtype: Local Sting Reaction
  description: >-
    Redness at the sting site accompanies the immediate local reaction.
  phenotype_term:
    preferred_term: Erythema
    term:
      id: HP:0010783
      label: Erythema
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "accompanied by redness and the development of raised wheals and white pustules at the sting site"
    explanation: Supports erythema at the sting site as part of the typical local reaction.
- name: Urticaria
  category: Dermatologic
  frequency: FREQUENT
  description: >-
    Urticaria or papules were recorded in 33.33% of assembled cases. Local
    urticarial and erythematous change follows the initial lesion, and
    generalized urticaria beyond the sting site indicates a systemic allergic
    reaction.
  phenotype_term:
    preferred_term: Urticaria
    term:
      id: HP:0001025
      label: Urticaria
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "2,916 (33.33%) presented with urticaria or papules"
    explanation: "Quantitative basis for the FREQUENT band: urticaria or papules were recorded in 33.33% of cases, within the 30-79% range."
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "followed by IgE-mediated urticarial and erythematous reactions"
    explanation: Supports the urticarial component as IgE-mediated rather than part of the direct alkaloid injury.
  notes: >-
    Deliberately not scoped to a subtype. The reported category spans local
    urticarial change after an ordinary sting and generalized urticaria as part of
    a systemic reaction, and the source does not separate them.
- name: Papule
  category: Dermatologic
  description: >-
    Papules are recorded in the same category as urticaria and are not separately
    quantified.
  phenotype_term:
    preferred_term: Papule
    term:
      id: HP:0200034
      label: Papule
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "2,916 (33.33%) presented with urticaria or papules"
    explanation: Supports papules as a reported lesion, recorded in a combined category with urticaria.
- name: Venom-induced anaphylaxis
  category: Immunologic
  subtype: Fire Ant Venom Anaphylaxis
  description: >-
    An IgE-mediated systemic reaction to fire ant venom, the form of this disease
    that causes death. Reported rates differ by roughly an order of magnitude
    between sources, so no frequency band is assigned; see the entry notes.
  phenotype_term:
    preferred_term: Venom-induced anaphylaxis
    term:
      id: HP:0500096
      label: Venom-induced anaphylaxis
  evidence:
  - reference: PMID:40230786
    reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fire ant and flying Hymenoptera-venom anaphylaxis prevalence in the general population was 0.048% and 0.083%, respectively."
    explanation: Supports fire ant venom anaphylaxis as a measured clinical entity with a population prevalence.
  - reference: PMID:37624246
    reference_title: "Chemistry and Functions of Imported Fire Ant Venom."
    supports: SUPPORT
    quote_role: REVIEW_SYNTHESIS
    evidence_source: OTHER
    snippet: "Systemic allergic reactions to fire ant stings are observed in approximately 2% of victims"
    explanation: Independent estimate of the proportion of stung people who react systemically, quoted here because it differs from the other reported figures.
- name: Anaphylactic shock
  category: Cardiovascular
  subtype: Fire Ant Venom Anaphylaxis
  frequency: VERY_RARE
  description: >-
    Circulatory collapse was recorded in 1.17% of assembled cases. It is nested
    within the systemic-allergy category rather than being independent of it.
  phenotype_term:
    preferred_term: Anaphylactic shock
    term:
      id: HP:0100845
      label: Anaphylactic shock
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "173 (1.98%) experienced dizziness or headache, 102 (1.17%) suffered shock"
    explanation: "Quantitative basis for the VERY_RARE band: shock was recorded in 1.17% of cases, within the 1-4% range."
- name: Laryngeal edema
  category: Respiratory
  subtype: Fire Ant Venom Anaphylaxis
  description: >-
    Upper airway swelling during a systemic reaction, with the attendant risk of
    obstruction. Not separately quantified in the reported series.
  phenotype_term:
    preferred_term: Laryngeal edema
    term:
      id: HP:0012027
      label: Laryngeal edema
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "potentially leading to laryngeal edema, asthma, respiratory distress, or even anaphylactic shock"
    explanation: Supports laryngeal edema as a documented manifestation of the systemic allergic reaction.
- name: Fever
  category: Constitutional
  frequency: VERY_RARE
  description: >-
    Fever was recorded in 2.65% of assembled cases.
  phenotype_term:
    preferred_term: Fever
    term:
      id: HP:0001945
      label: Fever
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "658 cases (7.52%) developed systemic allergy, 232 (2.65%) had fever"
    explanation: "Quantitative basis for the VERY_RARE band: fever was recorded in 2.65% of cases, within the 1-4% range."
- name: Headache
  category: Neurologic
  frequency: VERY_RARE
  description: >-
    Dizziness or headache, recorded as a combined category, occurred in 1.98% of
    assembled cases.
  phenotype_term:
    preferred_term: Headache
    term:
      id: HP:0002315
      label: Headache
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "173 (1.98%) experienced dizziness or headache"
    explanation: "Quantitative basis for the VERY_RARE band: the combined dizziness-or-headache category was recorded in 1.98% of cases."
- name: Lymphadenopathy
  category: Hematologic
  description: >-
    Localized allergic lymphadenopathy was recorded in 0.94% of assembled cases,
    below the lowest frequency band, so no band is assigned.
  phenotype_term:
    preferred_term: Lymphadenopathy
    term:
      id: HP:0002716
      label: Lymphadenopathy
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "82 (0.94%) exhibited localized allergic lymphadenopathy"
    explanation: Supports localized allergic lymphadenopathy as a reported manifestation, at a frequency below 1%.
environmental:
- name: Fire ant sting on nest disturbance
  description: >-
    The ordinary route of exposure is disturbing an occupied mound, after which
    workers swarm and sting repeatedly. Risk follows ant distribution, nest
    density and human contact, so outdoor work, agriculture and infested green
    space matter more than any host factor.
  exposure_term:
    preferred_term: exposure to Solenopsis venom by fire ant sting
    term:
      id: ECTO:0000537
      label: exposure to toxin
    qualifiers:
    - predicate:
        preferred_term: has input
        term:
          id: RO:0002233
          label: has input
      value:
        preferred_term: solenopsin A
        term:
          id: CHEBI:80722
          label: (-)-Solenopsin A
  effect: Injects venom into skin, initiating both the alkaloid and the protein branch of the disease.
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "When a RIFA nest is disturbed, the workers rapidly swarm out to attack the intruder using their stings and venom"
    explanation: Supports nest disturbance followed by swarming attack as the ordinary exposure route.
  - reference: PMID:37355195
    reference_title: "Envenomation From Flood-Related Fire Ant Rafting: A Cautionary Note."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Imported fire ants aggressively sting humans, leading to a variety of local and systemic effects."
    explanation: Supports aggressive stinging of humans as the exposure event behind both local and systemic disease.
  notes: >-
    No ECTO class binds this exposure precisely. Searched the local ECTO build on
    2026-10-06 with `runoak -i sqlite:obo:ecto info` for `l~venom`, `l~sting`,
    `l~bite`, `l~arthropod`, `l~insect`, `l~envenom`, `l~hymenoptera` and
    `l~animal`. The first six return no ECTO term at all; `l~insect` returns only
    insecticide-exposure classes such as ECTO:9000089; `l~animal` returns only
    animal-waste and manure classes. ECTO:0000537 exposure to toxin is therefore
    bound as the nearest true parent, with the specificity carried in
    `preferred_term` and the venom alkaloid attached as a qualifier. This follows
    the convention already used by the sibling envenomation entries
    Scorpion_Envenomation and Black_Widow_Spider_Envenomation, which bind
    ECTO:0000537 and ECTO:0000730 the same way.
  influences_mechanisms:
  - target: Fire ant sting and venom deposition in skin
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: The sting is the physical act that deposits venom in the skin.
    evidence:
    - reference: PMID:42302087
      reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "When a RIFA nest is disturbed, the workers rapidly swarm out to attack the intruder using their stings and venom"
      explanation: Supports the exposure initiating the venom deposition step of the mechanism.
- name: Flood-related contact with rafting fire ant colonies
  description: >-
    Fire ants survive flooding by linking into floating rafts, which brings whole
    colonies into contact with people wading or boating in flooded areas. This is
    an exposure route created by the ants' own behavioural adaptation rather than
    by nest disturbance.
  exposure_term:
    preferred_term: exposure to Solenopsis venom from a rafting colony during flooding
    term:
      id: ECTO:0000537
      label: exposure to toxin
  environment_context:
    preferred_term: flood plain
    term:
      id: ENVO:00000255
      label: flood plain
  effect: Creates high-dose, multi-sting exposure opportunities during flood conditions.
  evidence:
  - reference: PMID:37355195
    reference_title: "Envenomation From Flood-Related Fire Ant Rafting: A Cautionary Note."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fire ants display a behavioral adaptation to survive flooding, called \"rafting,\" bringing humans into even more contact with fire ants."
    explanation: Directly supports rafting during flooding as a distinct route to increased human contact and envenomation.
  influences_mechanisms:
  - target: Fire ant sting and venom deposition in skin
    environmental_effect: TRIGGERS
    causal_link_type: DIRECT
    description: Contact with a floating colony delivers multiple simultaneous stings.
    evidence:
    - reference: PMID:37355195
      reference_title: "Envenomation From Flood-Related Fire Ant Rafting: A Cautionary Note."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Imported fire ants aggressively sting humans, leading to a variety of local and systemic effects."
      explanation: Supports the rafting exposure route producing the same stinging injury.
treatments:
- name: Epinephrine for systemic reactions
  description: >-
    Epinephrine is the first-line treatment for a systemic reaction, and prompt
    administration is the intervention that prevents death. Underuse is a
    documented problem: fire ant venom anaphylaxis in systemic mastocytosis is
    frequently misdiagnosed and not treated with epinephrine.
  therapeutic_modality: SMALL_MOLECULE
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
    therapeutic_agent:
    - preferred_term: epinephrine
      term:
        id: CHEBI:33568
        label: adrenaline
  target_mechanisms:
  - target: IgE-mediated mast cell activation on re-exposure
    treatment_effect: MODULATES
    description: >-
      Epinephrine opposes the physiological consequences of mediator release
      rather than preventing degranulation, reversing vasodilation, capillary
      leak and bronchoconstriction.
    evidence:
    - reference: PMID:40230786
      reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
      supports: SUPPORT
      directness: INDIRECT
      evidence_source: HUMAN_CLINICAL
      snippet: "Fire ant-venom anaphylaxis in systemic mastocytosis is frequently misdiagnosed and not treated with epinephrine."
      explanation: >-
        Graded INDIRECT because the source establishes epinephrine as the
        expected treatment for this reaction by reporting its omission as a
        deficiency, rather than measuring its effect on the mast cell mediator
        mechanism.
  evidence:
  - reference: PMID:40230786
    reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Fire ant-venom anaphylaxis in systemic mastocytosis is frequently misdiagnosed and not treated with epinephrine."
    explanation: Supports both the expected role of epinephrine and the documented failure to give it in the highest-risk group.
- name: Fire ant whole-body extract venom immunotherapy
  description: >-
    Whole-body extract immunotherapy is the only disease-modifying treatment for
    fire ant venom allergy. In a multisite retrospective review, 85.7% of patients
    who had previously had a systemic reaction and who reached maintenance had no
    worse than a large local swelling after a subsequent sting, while only 2.9%
    had a systemic reaction to the immunotherapy itself.
  therapeutic_modality: OTHER
  treatment_term:
    preferred_term: fire ant whole-body extract immunotherapy
    term:
      id: NCIT:C15262
      label: Immunotherapy
  target_mechanisms:
  - target: Mast cell arming by venom-specific IgE
    treatment_effect: MODULATES
    description: >-
      Immunotherapy changes the immune response to the venom allergens so that
      re-exposure produces a much attenuated reaction.
    evidence:
    - reference: PMID:37781270
      reference_title: "Multisite evaluation of fire ant venom immunotherapy safety and efficacy."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Imported fire ant (IFA) venom immunotherapy (VIT) is the only disease-modifying treatment reported to be effective at decreasing the risk of systemic reactions (SRs) to IFA stings."
      explanation: Supports immunotherapy acting on the sensitized state itself, which is what makes it disease-modifying rather than symptomatic.
  evidence:
  - reference: PMID:37781270
    reference_title: "Multisite evaluation of fire ant venom immunotherapy safety and efficacy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "A substantial proportion of patients undergoing IFA VIT experienced protection against anaphylaxis with reexposure, with relatively few adverse events."
    explanation: Supports both efficacy against anaphylaxis on re-exposure and an acceptable adverse-event rate.
  - reference: PMID:37781270
    reference_title: "Multisite evaluation of fire ant venom immunotherapy safety and efficacy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "85.7% (24 of 28) of the subjects noted symptoms no worse than a large swelling reaction after a repeat IFA sting. Notably, only 2.9% of the subjects (4 of 137) had an SR due to VIT."
    explanation: Quantifies both the protective effect on re-sting and the rate of systemic reactions caused by the treatment itself.
  - reference: PMID:40230786
    reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "whole-body extract IT (WBE-IT) is effective in the treatment of FA-venom anaphylaxis"
    explanation: Independent support for whole-body extract immunotherapy as effective treatment for the anaphylactic form.
- name: Avoidance of occupied mounds and repeated stings
  description: >-
    Because the venom is already injected by the time the disease begins,
    prevention is exposure reduction: avoiding occupied nests, and for a person
    with a previous systemic reaction, carrying prescribed epinephrine.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: fire ant exposure avoidance
    term:
      id: NCIT:C15900
      label: Lifestyle Therapy
  target_mechanisms:
  - target: Fire ant sting and venom deposition in skin
    treatment_effect: INHIBITS
    description: Avoiding contact prevents the venom deposition that initiates the disease.
    evidence:
    - reference: PMID:37355195
      reference_title: "Envenomation From Flood-Related Fire Ant Rafting: A Cautionary Note."
      supports: SUPPORT
      directness: INDIRECT
      evidence_source: HUMAN_CLINICAL
      snippet: "Fire ants display a behavioral adaptation to survive flooding, called \"rafting,\" bringing humans into even more contact with fire ants."
      explanation: >-
        Graded INDIRECT because the source identifies contact as the modifiable
        step and names a circumstance that increases it, rather than measuring the
        effect of an avoidance intervention.
  evidence:
  - reference: PMID:42302087
    reference_title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "There is an urgent need for enhanced protective measures and treatment options."
    explanation: Supports protective measures as a recognized need in affected regions.
diagnosis:
- name: Venom sensitization testing after a systemic reaction
  description: >-
    After a systemic reaction, sensitization is confirmed by skin testing with
    whole-body extract or by serum venom-specific IgE. In a mastocytosis cohort,
    13 of 14 patients with a clinical history of fire ant venom anaphylaxis had
    evidence of sensitization by one or the other. The test confirms
    sensitization rather than predicting who will react, since sensitization
    rates in colonized regions far exceed the anaphylaxis prevalence.
  diagnosis_term:
    preferred_term: venom skin testing
    term:
      id: NCIT:C17137
      label: Skin Test
  evidence:
  - reference: PMID:40230786
    reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Thirteen of 14 patients with a clinical history of FA-venom anaphylaxis had evidence of sensitization by skin testing or serum specific-IgE testing."
    explanation: Supports skin testing and serum specific-IgE as the confirmatory tests, with their yield in a clinically characterized cohort.
  - reference: PMID:37781270
    reference_title: "Multisite evaluation of fire ant venom immunotherapy safety and efficacy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The in vitro IFA sensitization rates in our prospective cohort ranged from 19.1% to 24.1%."
    explanation: Quantifies in vitro sensitization rates, which is the background against which a positive result has to be interpreted.
- name: Serum venom-specific IgE measurement
  description: >-
    Serum fire ant specific IgE is measured alongside total IgE and tryptase. A
    positive result establishes sensitization; total IgE is measured so that a
    high background level is not mistaken for specific sensitization.
  diagnosis_term:
    preferred_term: venom-specific immunoglobulin E measurement
    term:
      id: NCIT:C81970
      label: Immunoglobulin E Measurement
  evidence:
  - reference: PMID:37781270
    reference_title: "Multisite evaluation of fire ant venom immunotherapy safety and efficacy."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Serum was tested for IFA IgE via ICAP as well as by measuring tryptase and total IgE levels"
    explanation: Supports the specific-IgE assay performed together with tryptase and total IgE.
- name: Basal serum tryptase for mastocytosis screening
  description: >-
    Because systemic mastocytosis is a major risk factor for severe venom
    anaphylaxis, a patient with a systemic reaction is screened for it by
    examination for cutaneous mastocytosis lesions and by a basal serum
    tryptase-based risk score. Nearly half of fire ant venom anaphylaxis episodes
    in that cohort were not initially recognized as anaphylaxis at all, which is
    the practical reason this screening matters.
  diagnosis_term:
    preferred_term: basal serum tryptase measurement
    term:
      id: NCIT:C92292
      label: Tryptase Measurement
  evidence:
  - reference: PMID:40230786
    reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Patients with FH anaphylaxis are screened for SM by a) physical exam to identify monomorphic lesions of maculopapular cutaneous mastocytosis, b) calculation of a symptom- and basal serum tryptase (BST)-based risk scoring tool"
    explanation: Supports the stated screening pathway for systemic mastocytosis after venom anaphylaxis.
  - reference: PMID:40230786
    reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Nearly half of all episodes of FA-venom anaphylaxis were not initially diagnosed as anaphylaxis or treated with epinephrine"
    explanation: Supports under-recognition of the reaction itself, which is what makes systematic screening after an episode necessary.
differential_diagnoses:
- name: Flying Hymenoptera venom anaphylaxis
  distinguishing_features:
  - Both produce IgE-mediated venom anaphylaxis, so the systemic presentations overlap closely
  - The fire ant sting leaves a characteristic sterile pustule that flying Hymenoptera stings do not
  - Fire ants deliver far less venom protein per sting, 10 to 100 ng against 2 to 20 micrograms for vespids
  - "Immunotherapy differs by preparation: fire ant allergy is treated with whole-body extract, flying Hymenoptera with venom extract"
  evidence:
  - reference: PMID:40230786
    reference_title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The amount of venom protein delivered in a single sting is highest in honey bee (25-150 mcg) and vespids (2-20 mcg) and lowest in FAs (10-100 ng)"
    explanation: Quantifies the venom protein dose difference that distinguishes fire ant from flying Hymenoptera envenomation.
  - reference: PMID:28873251
    reference_title: "Imported fire ant envenomation: A clinicopathologic study of a recognizable form of arthropod assault reaction."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Skin reactions to the sting of the imported fire ant have characteristic clinicopathological features."
    explanation: Supports that the local fire ant lesion is distinctive enough to separate it from other arthropod stings.
notes: >-
  Two mechanisms, one sting. The reason this entry splits into two subtypes is
  that the venom's mass is over 95% piperidine alkaloid while its allergenic
  activity sits almost entirely in the minor protein fraction. The alkaloid branch
  is directly cytotoxic, needs no sensitization, happens to nearly everyone stung,
  and resolves; the protein branch requires prior sensitization, happens to a
  small minority, and is what causes death. Pooling them would average a
  near-universal nuisance with a rare emergency.

  Frequency bands come from one series and should be read with its ascertainment
  in mind. The percentages are from 8,749 cases assembled from 17 peer-reviewed
  papers, 13 news reports and one county hospital's emergency department in
  China. Three limits are stated by the authors themselves and are why the bands
  here are not population risks: the categories overlap, with shock nested inside
  systemic allergy, so they are not mutually exclusive; mild cases are
  underreported because most stung people never seek care; and unrecorded
  instances of the five serious symptoms were counted as absent rather than
  missing.

  No frequency band is assigned to venom-induced anaphylaxis, because the
  available figures disagree by about an order of magnitude and the disagreement
  cannot be resolved from these sources. The Chinese series records systemic
  allergy in 7.52% of cases; a venom-chemistry review states approximately 2% of
  victims; and the same Chinese paper quotes an earlier study at 0.5 to 2%.
  Separately, the measured population prevalence of the anaphylactic form in US
  Tricare beneficiaries is 0.048%, which is a different quantity again, computed
  over everyone rather than over stung people. All of these are recorded, as
  prevalence records or as phenotype evidence, rather than averaged into a band.

  The speech-impediment phenotype is deliberately omitted. The source reports it
  in 0.75% of cases but describes it in two ways that map to different HPO terms,
  as a "speech impediment" and as having "temporarily lost their voice". Binding
  either Dysphonia or Aphasia would assert a specificity the source does not
  support, and no HPO term covers the ambiguity.

  One arithmetic discrepancy in a cited source, flagged here so nobody later
  quotes the wrong figure. The abstract of the Chinese series projects 526,000
  people annually with systemic allergy, while its own results section gives
  approximately 0.0526 million, that is 52,600. The results figure is the one
  consistent with the paper's other projections. This entry cites no projected
  national totals from that paper, only its observed case counts and percentages,
  so the discrepancy does not propagate into the knowledge base.

  Mastocytosis is a host modifier, not a cause. Systemic mastocytosis is a major
  risk factor for severe venom anaphylaxis, and acquired mast cell disease
  frequently carries somatic KIT p.D816V, but that variant is a feature of the
  mast cell neoplasm and not a susceptibility allele for fire ant poisoning.
  There is no causal human gene for this disease and the entry carries no genetic
  section. The venom allergen names Sol i 1 to Sol i 4 are ant proteins, not human
  gene symbols.
references:
- reference: PMID:42302087
  title: "Analysis of the human health threat caused by the red imported fire ant in mainland China."
- reference: PMID:40230786
  title: "Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis."
- reference: PMID:37781270
  title: "Multisite evaluation of fire ant venom immunotherapy safety and efficacy."
- reference: PMID:37624246
  title: "Chemistry and Functions of Imported Fire Ant Venom."
- reference: PMID:37355195
  title: "Envenomation From Flood-Related Fire Ant Rafting: A Cautionary Note."
- reference: PMID:30258210
  title: "The allergic response mediated by fire ant venom proteins."
- reference: PMID:28873251
  title: "Imported fire ant envenomation: A clinicopathologic study of a recognizable form of arthropod assault reaction."
📚

References & Deep Research

References

7
PMID:42302087
Analysis of the human health threat caused by the red imported fire ant in mainland China.
No top-level findings curated for this source.
PMID:40230786
Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis.
No top-level findings curated for this source.
PMID:37781270
Multisite evaluation of fire ant venom immunotherapy safety and efficacy.
No top-level findings curated for this source.
PMID:37624246
Chemistry and Functions of Imported Fire Ant Venom.
No top-level findings curated for this source.
PMID:37355195
Envenomation From Flood-Related Fire Ant Rafting: A Cautionary Note.
No top-level findings curated for this source.
PMID:30258210
The allergic response mediated by fire ant venom proteins.
No top-level findings curated for this source.
PMID:28873251
Imported fire ant envenomation: A clinicopathologic study of a recognizable form of arthropod assault reaction.
No top-level findings curated for this source.

Deep Research

1

Deep research results are used as seeds for research; they do not undergo the same validation as the main records and may contain errors. How we use deep research.

Evaluations and curation notes (2)

Review round 1: Fire Ant Poisoning · 2026-10-06T23:28:31Z · View source

Addressed the ai4c-reviewer round on PR #13632 in one push. CRITICAL (item 1), confirmed and root-caused. references_cache/PMID_42302087.md was genuinely not committed, and CI proved the consequence: it re-fetched the reference, got abstract-only where the local cache holds full text, and 30 snippets failed. The PR body's '75/75 verified' was true locally and false on a fresh checkout, which is exactly the silent-network-fetch failure CLAUDE.md warns about. The cause was a shell bug worth recording because it was not specific to this entry: the staging loop was 'while read r; do git add ...; done < cited.txt' over a list written with "\n".join(...) and no trailing newline. 'read' returns false on an unterminated final line, so the loop body never ran for it and git add was never called, silently. The dropped file was the alphabetically last cited PMID in each of three PRs opened in the same session (#13631 PMID_988568, #13632 PMID_42302087, #13633 PMID_40913680). All three are being corrected. Staging is now verified with 'git ls-files --error-unmatch' per cited reference rather than trusted. IMPORTANT (item 2), accepted in full. Four snippets taken from the Introduction of PMID:30258210 were graded MODEL_ORGANISM although none is a result of the mouse experiments. All four now carry quote_role: BACKGROUND with evidence_source regraded from what the quoted sentence describes: the >95%-alkaloid sentence, the stereotypical-second-exposure sentence and the life-threatening-anaphylaxis sentence are HUMAN_CLINICAL + BACKGROUND, and the Th2/IL-4 clonal-expansion sentence is OTHER + BACKGROUND as general immunology. The reviewer's further point that the Th2/IL-4 snippet never mentions IgE was also taken: the IgE class-switching edge now leads with the figure-legend sentence naming IgE-secretory plasma cells and mast-cell binding, graded directness: INDIRECT because it is the authors' hypothesized scheme rather than a measurement, with the IL-4 sentence retained behind it as explicitly INDIRECT context. The paper's genuine results (footpad swelling, eosinophil recruitment with eotaxin, MHCII/CD86 upregulation, the abstract conclusion) now carry quote_role: PRIMARY_RESULT, since they have been assessed. Suggestion 3 taken: the bundled 'Venom-specific IgE production and mast cell arming' node is split into 'Venom-specific IgE class switching' (MOLECULAR, B cell, immunoglobulin production) and 'Mast cell arming by venom-specific IgE' (CELLULAR, mast cell). This removes the scale/cell-type inconsistency the reviewer identified rather than only picking one scale. The immunotherapy target_mechanisms link was retargeted onto the arming node, which is the state it acts on. Suggestion 4 taken: the process narration was removed from the cytotoxicity node's notes, keeping the substantive claim (murine BMDC origin of the figure, no Wnt/MAPK/mTOR lesion asserted, isolated-solenopsin cancer-cell data do not transfer) and dropping the reference to the deep-research report. Suggestion 6 taken: quote_role: REVIEW_SYNTHESIS added to the four PMID:37624246 items. Suggestion 5 partly taken. Death is added as a progression phase (3/8,749, 0.03%) together with the source's own attribution of most fatalities to delayed or inadequate treatment, which connects it to the documented undertreatment with epinephrine. A diagnosis: block is added with three entries: venom skin testing (NCIT:C17137), venom-specific IgE measurement (NCIT:C81970) and basal serum tryptase for mastocytosis screening (NCIT:C92292), all reachable from NCIT:C25218 and evidenced from references already cached in this PR. Symptomatic local care, rhabdomyolysis and acute kidney injury after mass stinging, and secondary infection are NOT added: no quotable statement for any of them exists in the seven references cached here, and adding them would mean either an unevidenced claim or a further reference round. They are left for a follow-up rather than asserted. One self-inflicted error caught during this round: inserting the new progression phase introduced a second top-level 'progression:' key, which just check-duplicate-keys flagged. The blocks were merged into the existing one; the gate now passes. Validation after the fixes, run to completion and read: just validate-disorders (85 snippets, 92 titles, 0 issues), just validate-terms (passed), just count-verified-snippets (85/85), just check-entity-refs (OK), just check-causal-targets (no new broken targets), just check-duplicate-keys (OK after the merge), just check-snippet-grading (no new divergences). Every cited reference's cache file was then verified staged with git ls-files --error-unmatch. conf/ is unmodified.

Create: Fire Ant Poisoning · 2026-10-06T22:56:58Z · View source

New Disease entry for fire ant poisoning (MONDO:0100341), curated as two has_subtypes because one sting drives two mechanistically separate diseases: a direct alkaloid cytotoxic injury (Local Sting Reaction) and an IgE-mediated systemic allergy (Fire Ant Venom Anaphylaxis). Deep research: Edison Falcon (research/Fire_Ant_Poisoning-deep-research-falcon.md, 11/11 references verified, confabulation_rate 0.0). Its needs_review flag was set only for a label variant on the supplied MONDO term, not a content defect. The report was used as a lead set; all citations were re-fetched and snippet-verified and all CURIEs were looked up in OAK while writing. The report earned its keep twice: it caught an arithmetic discrepancy in the abstract of its own key source (projected systemic-allergy cases given as 526,000 in the abstract versus 0.0526 million = 52,600 in that paper's results), and it warned against importing solenopsin cancer-cell signalling-pathway claims (Wnt/MAPK/mTOR) into clinical envenomation. Both warnings were acted on: no projected national totals from that paper are cited anywhere in the entry, and no such pathway is asserted. Pathograph: 7 nodes, one connected component, no orphans, single root entered via environmental influences_mechanisms. Alkaloid branch: sting and venom deposition -> piperidine alkaloid cytotoxic injury -> neutrophilic dermal infiltration with collagen degeneration -> sterile subepidermal pustule. Protein branch, in parallel from the same node: venom protein antigen presentation and type 2 sensitization -> venom-specific IgE production and mast cell arming -> IgE-mediated mast cell activation on re-exposure -> urticaria, venom-induced anaphylaxis, laryngeal edema, anaphylactic shock. Two prevalence records for the anaphylactic subtype from a Tricare beneficiary study: 0.048% general population and 0.085% in the 14 colonized states, both BAND_1_5_PER_10000 with rate_per_100000 and POPULATION denominator. Deliberate decisions, all recorded in the entry's notes: (1) Frequency bands are taken from one 8,749-case series and the entry records the three ascertainment limits its own authors state (overlapping categories with shock nested in systemic allergy, underreporting of mild cases, unrecorded serious symptoms counted as absent). (2) No frequency band on venom-induced anaphylaxis, because three sources give 7.52%, ~2% and 0.5-2% and the disagreement is not resolvable here; all are recorded rather than averaged. (3) The speech-impediment phenotype is omitted because the source describes it both as a speech impediment and as temporary loss of voice, which map to different HPO terms, and binding either would assert unsupported specificity. (4) No genetic section: mastocytosis is a host modifier and KIT p.D816V belongs to the mast cell neoplasm, not to this disease; Sol i 1-4 are ant proteins, not human gene symbols. (5) Three edges carry directness: INDIRECT where the source establishes a treatment or exposure relationship by implication rather than measurement. Ontology note: no ECTO class binds a sting or venom exposure. Eight searches of the local ECTO build are named verbatim in the environmental entry's notes along with what each returned, and ECTO:0000537 exposure to toxin is bound as the nearest true parent with the specificity in preferred_term, following the convention already used by Scorpion_Envenomation and Black_Widow_Spider_Envenomation. Two errors were caught and fixed during curation, both worth recording. A pre-write hook block caught an unquoted colon inside a differential_diagnoses distinguishing_features list item, which YAML had parsed as a mapping. And a programmatic title audit against references_cache caught a fabricated reference_title for PMID:42302087 that I had written from memory: it appeared 32 times and read entirely plausibly. It was replaced from the cache file's own title line by script, and a re-run confirmed 7/7 titles now match. Validation run and read: just validate (0 issues), just validate-terms (passed), just count-verified-snippets (75/75), just check-entity-refs (OK), just check-causal-targets (no new broken targets), just check-duplicate-keys (OK), just check-qualifier-terms (1 label matches; 1 RO term unvalidatable), just check-coarse-phenotypes (no new unexplained bindings), just check-term-cache-integrity (OK), and the authoritative just validate-disorders batch (75 snippets, 82 titles, 0 issues). New terms were seeded by pointing conf/oak_config.yaml at local sqlite adapters for the validator run and then restoring it; conf/ is unmodified in the diff.

Falcon ▸
Disease Characteristics Research Template
Edison Scientific Literature 52 citations 2026-10-06T17:58:05.242996

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

  • Disease Name: Fire Ant Poisoning
  • MONDO ID: MONDO:0100341 (if available)
  • Category: Injury

Research Objectives

Please provide a comprehensive research report on Fire Ant Poisoning covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

  • What is the disease? Provide a concise overview.
  • What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
  • What are the common synonyms and alternative names?
  • Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

  • Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
  • Risk Factors:

    Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

  • Genetic risk factors (causal variants, susceptibility loci, modifier genes)
  • Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
  • Protective Factors:

    Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

  • Genetic protective factors (protective variants, modifier alleles)
  • Environmental protective factors (diet, lifestyle, exposures that reduce risk)
  • Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

    Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

  • Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

    Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

  • Pathogenic Variants:
  • Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
  • Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
  • Variant type/class (missense, frameshift, nonsense, splice-site, structural)
  • Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
  • Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
  • Functional consequences (loss of function, gain of function, dominant negative)
  • Modifier Genes: Genes that modify disease severity or expression
  • Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

    Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

  • Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

    Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

  • Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

    Search first: CDC databases, WHO, PubMed, NHANES

  • Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

    Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

Present this section as an ordered causal chain first, then the detail below. Open with a numbered sequence of mechanistic steps running from the initiating lesion (mutation, exposure, infection) to the clinical manifestation, one step per line, each naming what it causes next. State the causal verb explicitly ("leads to", "results in") and say where a step is inferred rather than demonstrated. Where the mechanism branches, show the branch. The categories below are a checklist of what to cover within those steps, not the organizing structure — a step may draw on several of them, and a category may contribute to several steps.

  • Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

    Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

  • Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

    Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

  • Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

    Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

  • Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

    Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

  • Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

    Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

  • Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

    Search first: PubMed, Gene Ontology, Reactome

  • Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

    Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

  • Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

    Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

  • Molecular Profiling (if available):
  • Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
  • Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
  • Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
  • Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
  • Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
  • Advanced Technologies (if applicable):
  • Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
  • Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
  • Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
  • Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

  • Organ Level:
  • Primary organs directly affected
  • Secondary organ involvement (complications, secondary effects)
  • Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

    Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

  • Tissue and Cell Level:
  • Specific tissue types affected (epithelial, connective, muscle, nervous)
  • Specific cell populations targeted (with Cell Ontology terms)

    Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

  • Subcellular Level:
  • Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

    Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

  • Localization:
  • Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
  • Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

  • Onset:
  • Typical age of onset (congenital, pediatric, adult, geriatric)
  • Onset pattern (acute, subacute, chronic, insidious)

    Search first: OMIM, Orphanet, HPO, PubMed

  • Progression:
  • Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
  • Progression rate (rapid, slow, variable)
  • Disease course pattern (episodic, relapsing-remitting, progressive, stable)
  • Disease duration (self-limited, chronic lifelong)

    Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

  • Patterns:
  • Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
  • Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

  • Epidemiology:
  • Prevalence (cases per 100,000 at given time)
  • Incidence (new cases per 100,000 per year)

    Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

  • For Genetic Etiology:
  • Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
  • Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
  • Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
  • Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
  • Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
  • Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
  • Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
  • Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
  • Population Demographics:
  • Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
  • Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
  • Geographic distribution of specific variants
  • Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
  • Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

  • Clinical Tests:
  • Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
  • Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
  • Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
  • Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
  • Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
  • Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
  • Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
  • Genetic Testing:

    Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

  • Overview of recommended genetic testing approach
  • Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
  • Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
  • Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
  • Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
  • Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
  • Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
  • FISH > Search first: ClinVar, cytogenetics databases, PubMed
  • Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
  • Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
  • Omics-Based Diagnostics (if applicable):
  • RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
  • Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
  • Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
  • Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
  • Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
  • Clinical Criteria:
  • Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
  • Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
  • Screening:
  • Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

  • Survival and Mortality:
  • Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
  • Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
  • Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
  • Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
  • Morbidity and Function:
  • Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
  • Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
  • Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
  • Disease Course:
  • Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
  • Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
  • Prediction:
  • Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
  • Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

  • Pharmacotherapy:
  • Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
  • Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
  • Advanced Therapeutics:
  • Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
  • Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
  • RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
  • Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
  • Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
  • Surgical and Interventional:
  • Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
  • Supportive and Rehabilitative:
  • Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
  • Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
  • Experimental:
  • Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
  • Treatment Outcomes:
  • Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
  • Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
  • Treatment Strategy:
  • Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
  • Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
  • Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest NCIT (NCI Thesaurus) clinical-intervention terms where applicable.

13. Prevention

  • Prevention Levels:
  • Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
  • Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
  • Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
  • Immunization: Vaccine strategies (if applicable)

    Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

  • Screening and Early Detection:
  • Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
  • Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
  • Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
  • Behavioral Interventions: Lifestyle modifications to reduce risk

    Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

  • Counseling: Genetic counseling (risk assessment, family planning guidance)

    Search first: NSGC resources, ACMG guidelines, GeneReviews

  • Public Health:
  • Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
  • Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
  • Prophylaxis: Preventive medications or procedures

    Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

  • Taxonomy: Species affected (with NCBI Taxon identifiers)

    Search first: NCBI Taxonomy

  • Breed: Specific breeds affected (with VBO identifiers if applicable)

    Search first: VBO (Vertebrate Breed Ontology)

  • Gene: Orthologous genes in other species (with NCBI Gene IDs)

    Search first: NCBI Gene

  • Natural Disease:
  • Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
  • Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
  • Comparative Biology:
  • Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
  • Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
  • Transmission (if applicable):
  • Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
  • Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

  • Model Types:
  • Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
  • Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
  • Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
  • Genetic Models:
  • Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
  • Model Characteristics:
  • Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
  • Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
  • Applications:
  • Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
  • Resources:
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Citation Requirements

  • Cite primary literature (PMID preferred) for all mechanistic and clinical claims
  • Prioritize recent reviews and landmark papers
  • Include direct quotes from abstracts where possible to support key statements
  • Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, NCIT, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (NCIT terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Fire ant poisoning: disease-characteristics research report

Scope and evidence standard (6 October 2026). “Fire ant poisoning” is best treated as an acute, exposure-dependent sting/envenomation injury, not a single inherited disorder. The best-described agents are Solenopsis invicta (red imported fire ant), S. richteri (black imported fire ant), and, in some regions, S. geminata. Direct venom toxicity and allergic reactions can occur separately or together. Much of the precise human evidence concerns imported fire ants; findings for one species should not automatically be transferred to another. This synthesis prioritizes original human cohorts, an experimental mouse study, and 2023–2024 reviews; DOIs are supplied where the retrieved sources did not verify PMIDs. Suggested ontology labels below are mappings for curator verification, not assertions that a particular accession exists. (mcmurray2025fireantvenomanaphylaxis pages 2-3, sukprasert2012characterizationofthe pages 1-3, dioguardi2024therapeuticpotentialof pages 4-6)

1. Disease information and identifiers

A worker ant anchors itself with its jaws and injects venom with an abdominal stinger, potentially stinging repeatedly. The characteristic presentation is immediate local burning pain and erythema, followed by wheal, swelling and sometimes a sterile pustule. A susceptible person can instead, or also, develop a rapid systemic allergic reaction, including anaphylaxis. Appropriate synonyms include fire-ant sting, fire-ant envenomation, imported-fire-ant sting reaction, red-imported-fire-ant envenomation and, specifically for immune disease, fire-ant venom allergy; “bite” is common colloquial usage but is less precise for venom injection. (dioguardi2024therapeuticpotentialof pages 2-4, dioguardi2024therapeuticpotentialof pages 4-6, rodrigo2018immunotherapyinanaphylaxis pages 1-2)

Identifiers: The requested MONDO:0100341 is a candidate supplied by the requester, not independently verified as a current MONDO record in the retrieved material. MeSH D007299, “Insect Bites and Stings,” is verified in a ClinicalTrials.gov record and is broader than fire-ant poisoning. An exact species-specific ICD-10-CM/ICD-11 code, OMIM entry, Orphanet entry, disease-specific MeSH descriptor, SNOMED CT concept and formal HPO association were not independently verified; do not fabricate them. One human prevalence study found that using nonspecific Hymenoptera allergy ICD-10 codes alone substantially misclassified patients: only 36 of 150 reviewed records documented actual venom anaphylaxis. (NCT00435552 chunk 1, mcmurray2025fireantvenomanaphylaxis pages 5-7)

Data provenance: This entry synthesizes aggregated published cohorts, an individual-patient clinical cohort, experimental work and review literature. It is not a claim to have accessed the knowledge-base user's EHRs. A TRICARE analysis used administrative records with sampled chart validation, whereas a Brazilian immunotherapy study followed 33 clinically identified patients. (mcmurray2025fireantvenomanaphylaxis pages 1-2, watanabe2022clinicalandlaboratory pages 1-4)

2. Etiology, risks and protective factors

Necessary cause: Contact with, and venom injection by, a stinging fire ant. S. invicta venom is predominantly water-insoluble piperidine alkaloids, particularly solenopsins; smaller protein fractions include the allergenic Sol i 1–4 components. Estimates of approximately 95% alkaloids and 10–100 ng protein per sting come from compositional literature, not a measured dose for every patient. S. geminata has a related but nonidentical allergen, Sol gem 2. No infectious organism or primary human germline mutation is required. (sukprasert2012characterizationofthe pages 1-3, dioguardi2024therapeuticpotentialof pages 4-6)

Exposure risk rises with outdoor work, agriculture, infested urban green space, nest disturbance, repeated stings and expanding ant range. Immobility, very young or older age, cognitive impairment and flooding can increase opportunities for high-dose encounters; these are exposure/vulnerability factors, not proven fire-ant-specific genotype effects. Systemic mastocytosis is an important host condition to consider after severe reactions: among 97 persons with systemic mastocytosis or monoclonal mast-cell activation syndrome in a selected U.S. cohort, 14 had a fire-ant anaphylaxis history. This selected denominator must not be treated as risk among all stung persons. Existing sensitization permits IgE-mediated responses on subsequent exposure. (chen2026analysisofthe pages 2-4, mcmurray2025fireantvenomanaphylaxis pages 7-9, mcmurray2025fireantvenomanaphylaxis pages 9-10)

Protection is principally avoidance of occupied nests and repeated stings, rapid recognition and treatment of systemic reactions, ready access to prescribed epinephrine for people with prior anaphylaxis, and specialist whole-body-extract immunotherapy after an appropriate allergic evaluation. Evidence for a protective human allele, diet, supplement or established pharmacogenomic intervention specific to this injury was not retrieved. The plausible gene–environment interaction is that mast-cell disease alters the response to venom exposure; it does not turn envenomation into a Mendelian disorder. (watanabe2022clinicalandlaboratory pages 1-4, mcmurray2025fireantvenomanaphylaxis pages 7-9, rodrigo2018immunotherapyinanaphylaxis pages 4-5)

3. Phenotypes and quality-of-life impact

Clinical phenotypes occur at any age after exposure, with acute onset and highly variable severity. Immediate pain/wheal can evolve into local pruritus and a sterile pustule within approximately a day; large local reactions can last up to 72 hours. Systemic urticaria, respiratory compromise and cardiovascular shock require urgent assessment. Severe multi-sting toxicity, reported complications including rhabdomyolysis and acute kidney injury, and unusual eye injury should be documented separately from uncomplicated pustulation. Neither behavioral change nor a characteristic routine blood-test abnormality is an obligatory manifestation. (dioguardi2024therapeuticpotentialof pages 4-6, rodrigo2018immunotherapyinanaphylaxis pages 1-2, guillet2022partiinsect pages 3-4, chen2026analysisofthe pages 1-2)

The largest retrieved symptom compilation is a 2026 China analysis combining published reports, news and hospital cases. Its categories overlap and describe recorded cases, not the prevalence among all stung residents. The paper's results text and inspected image support the following counts; suggested HPO labels require curatorial verification. (chen2026analysisofthe pages 2-4, chen2026analysisofthe pages 6-8, chen2026analysisofthe media 303ec5e0)

Phenotype Patients / 8,749 Reported percent Suggested HPO term label
Itching and pain 6,784 77.54% Pruritus; Pain
Vesicles or pustules 3,160 36.12% Vesicle; Pustule
Urticaria or papules 2,916 33.33% Urticaria; Papule
Systemic allergy 658 7.52% Systemic anaphylaxis
Fever 232 2.65% Fever
Dizziness or headache 173 1.98% Dizziness; Headache
Shock 102 1.17% Anaphylactic shock
Localized allergic lymphadenopathy 82 0.94% Lymphadenopathy
Transient speech loss 66 0.75% Loss of speech
Death 3 0.03% Death
Ascertainment and interpretation Mixed hospital records, published studies, and online news reports—not a population-based sample Categories overlap; shock is nested within systemic allergy, so percentages are neither mutually exclusive nor population risks. Chen et al., 2026 (chen2026analysisofthe pages 6-8, chen2026analysisofthe media 303ec5e0)

Table: Clinical phenotypes among 8,749 assembled fire-ant sting cases reported by Chen et al. (2026). These mixed-source frequencies are descriptive rather than population-based; the corrected projected systemic-allergy count is 52,600, not the abstract's erroneous 526,000.

For knowledge-base annotation, classify itching/pain and dizziness/headache as symptoms; wheal, pustule, swelling, urticaria, fever, lymphadenopathy and speech impairment as clinical manifestations; hypotension/shock as severe signs; and, if clinically measured after massive envenomation, raised creatine kinase or renal dysfunction as complication-associated laboratory abnormalities rather than universal biomarkers. Candidate HPO labels additionally include Edema, Erythema, Hypotension, Dyspnea and Bronchospasm, where documented for the patient. Reliable age-stratified phenotype frequencies, quantitative EQ-5D/SF-36 scores and per-phenotype disability estimates were not established. Pain, itching and pustules may disrupt sleep or work; anaphylaxis can acutely interrupt normal function and creates a risk of future-exposure anxiety, but those quality-of-life effects should not be assigned invented fire-ant-specific numerical values. (watanabe2022clinicalandlaboratory pages 1-4, chen2026analysisofthe pages 1-2, dioguardi2024therapeuticpotentialof pages 4-6, chen2026analysisofthe pages 6-8)

4. Human genetics and molecular annotations

Causal human genes, pathogenic variants, ACMG classifications, inheritance, penetrance, carrier frequency, founder effects and chromosomal abnormalities: not applicable as defining features of this venom injury. The antigen names Sol i 1, Sol i 2, Sol i 3 and Sol i 4 describe ant venom proteins, not HGNC symbols for human disease genes. Sol i 1 has phospholipase activity, Sol i 3 is antigen-5-related, and Sol i 2 is an important allergen; S. geminata Sol gem 2 was characterized by electrophoresis and mass spectrometry as a native dimer. (mcmurray2025fireantvenomanaphylaxis pages 2-3, sukprasert2012characterizationofthe pages 1-3)

Relevant host modifier, not the cause of a sting: Acquired mast-cell disease frequently carries somatic KIT p.D816V. In the selected 97-person mastocytosis/monoclonal mast-cell activation cohort, 82/97 were KIT p.D816V-positive; this is not a prevalence estimate for fire-ant poisoning, nor evidence that the variant predicts an individual's reaction. Specific germline susceptibility loci, protective variants, epigenetic signatures and modifier allele frequencies for fire-ant poisoning were not established. Routine gene panels or genomic sequencing are therefore not disease diagnostics; investigation of mastocytosis, potentially including KIT testing, is a separate clinically indicated evaluation after concerning anaphylaxis. (mcmurray2025fireantvenomanaphylaxis pages 5-7, mcmurray2025fireantvenomanaphylaxis pages 7-9)

5. Environmental and lifestyle information

The pertinent environmental agent is injected Solenopsis venom, with risk strongly shaped by ant distribution, nest density and human contact. Farmland, lawns and green spaces, outdoor activities, and disturbance of mounds are more relevant than tobacco, alcohol, exercise or diet as putative causes. Neither ionizing radiation nor an infectious agent is part of the established causal definition. Invasion surveillance and ant control constitute exposure reduction rather than treatment of an already injected toxin. Suggested chemical-entity labels, pending ChEBI accession verification, are solenopsin A, piperidine alkaloid, histamine and epinephrine. (dioguardi2024therapeuticpotentialof pages 2-4, chen2026analysisofthe pages 2-4, dioguardi2024therapeuticpotentialof pages 4-6)

6. Mechanism and pathophysiology

Ordered causal chain. The two main downstream branches should remain distinct:

  1. Ant contact and sting leads to venom deposition in skin; repeated stings lead to greater exposure. (dioguardi2024therapeuticpotentialof pages 2-4)
  2. Venom alkaloids lead to direct local cytotoxic and inflammatory injury; this results in immediate burning, erythema and edema. The exact molecular target in human sting lesions is incompletely established. (sukprasert2012characterizationofthe pages 1-3, dioguardi2024therapeuticpotentialof pages 4-6)
  3. Local injury leads to neutrophil/eosinophil infiltration, fibrin deposition and basal tissue necrosis, resulting in a characteristic, often sterile pustule; this is the direct-toxicity branch and does not require prior IgE sensitization. (sukprasert2012characterizationofthe pages 1-3, dioguardi2024therapeuticpotentialof pages 4-6)
  4. In parallel, venom proteins lead to antigen presentation and type-2 sensitization; experimental mouse evidence demonstrates dendritic-cell activation, IL-4, eosinophil recruitment and eotaxin, whereas the full sequence to venom-specific IgE in a particular human is partly inferred from established allergy biology. (zamithmiranda2018theallergicresponse pages 6-7, zamithmiranda2018theallergicresponse pages 1-2)
  5. In a sensitized host, re-exposure leads to IgE-dependent mast-cell/basophil activation and mediator release; this results in generalized skin symptoms and, when severe, airway obstruction, bronchospasm or circulatory collapse. Specific cellular intermediates and mediator concentrations have not been measured for every fire-ant clinical phenotype. (zamithmiranda2018theallergicresponse pages 1-2, chen2026analysisofthe pages 1-2, mcmurray2025fireantvenomanaphylaxis pages 7-9)
  6. Heavy multi-sting exposure may lead to systemic toxic injury, resulting in reported muscle injury and kidney dysfunction; exact human dose–response, cellular target and contribution of allergy versus direct toxicity remain uncertain. (chen2026analysisofthe pages 1-2, guillet2022partiinsect pages 3-4)

Experimental resolution: In male BALB/c mice, venom-protein sensitization followed by challenge 14 days later caused footpad swelling, IL-4 production and eosinophilic recruitment; coadministration of venom proteins with ovalbumin increased ovalbumin responses, whereas heat-treated venom lost this adjuvant activity. The authors measured dendritic-cell MHC-II/CD86 up-regulation. These findings establish a protein-associated type-2 mechanism in an induced mouse model, not a validated predictive molecular signature in patients. Do not claim that IL-5, IL-13 or venom-specific IgE were quantified in that study on the basis of the retrieved results. (zamithmiranda2018theallergicresponse pages 6-7, daniel2018theallergicresponse pages 6-9, zamithmiranda2018theallergicresponse pages 7-8)

Annotation suggestions: GO biological-process labels inflammatory response, response to toxin, antigen processing and presentation, type-2 immune response, mast-cell activation, eosinophil chemotaxis and tissue necrosis; CL cell-type labels keratinocyte, neutrophil, eosinophil, dendritic cell, CD4-positive T cell, B cell, mast cell and basophil. These describe implicated or biologically plausible participants; not every cell type has been demonstrated in both human lesions and mouse models. Do not assert Wnt, MAPK, mTOR or PI3K–AKT as the established causal signaling pathway of clinical envenomation merely because isolated solenopsin has been investigated as a pharmacologic lead in unrelated cell and cancer models. No validated patient-specific transcriptomic, proteomic, metabolomic, lipidomic, spatial, single-cell, CRISPR-screen or epigenomic disease signature was retrieved. (zamithmiranda2018theallergicresponse pages 6-7, dioguardi2024therapeuticpotentialof pages 6-8, dioguardi2024therapeuticpotentialof pages 4-6)

7. Anatomical structures

Primary site: skin at the sting site, involving epidermis and superficial dermis; local swelling and pustules can occur on any exposed surface. Proposed UBERON label skin of body and CL labels keratinocyte, dermal immune cell, neutrophil and eosinophil require exact accession validation. Anaphylaxis can affect skin/mucosa, upper and lower airways and the cardiovascular circulation; reported complications involve skeletal muscle and kidney. Rare direct corneal stings affect the ocular surface. The site depends on exposure rather than a disease-specific left–right preference: lesions may be unilateral, bilateral or multifocal. (chen2026analysisofthe pages 1-2, dioguardi2024therapeuticpotentialof pages 2-4, dioguardi2024therapeuticpotentialof pages 4-6)

At subcellular level, secreted venom protein in extracellular tissue, surface immunoglobulin-receptor signaling and antigen processing by immune cells are mechanistic concepts; no fire-ant-specific diagnostic mitochondrial, nuclear, lysosomal or ER lesion was verified. Candidate GO cellular-component labels extracellular region, plasma membrane and antigen-processing compartment should be curated against individual experiments rather than assigned indiscriminately. (zamithmiranda2018theallergicresponse pages 6-7, zamithmiranda2018theallergicresponse pages 1-2)

8. Temporal development

Onset is acute after a sting at any life stage, not congenital. Burning and wheal are immediate; pustulation commonly develops by approximately 24 hours, while local pruritus and large local swelling can last up to 72 hours. The potential for rapid anaphylaxis makes the period immediately after a systemic reaction critical for emergency treatment. Most uncomplicated localized injuries are self-limited; persistent lesions, secondary infection, ocular injury and recurrent reactions on later exposures change the course. There is no recognized early/intermediate/end-stage classification, genetic anticipation or permanent remission guarantee after allergy treatment. Longer-term outcomes and relapse rates after stopping imported-fire-ant immunotherapy remain less well quantified than short-term field-sting outcomes. (dioguardi2024therapeuticpotentialof pages 4-6, rodrigo2018immunotherapyinanaphylaxis pages 1-2, guillet2022partiinsect pages 3-4, watanabe2022clinicalandlaboratory pages 13-16)

9. Population, epidemiology and inheritance

In a U.S. TRICARE direct-care population of 2,835,948, investigators estimated 1,370 fire-ant-anaphylaxis cases, 0.048% or approximately 48 per 100,000, and 0.085% or 85 per 100,000 within 14 states colonized by fire ants. These are estimates of anaphylaxis prevalence in a particular administrative population, not all sting poisoning, and are sensitive to coding, prescribing and military-associated exposure. In that cohort, 878 fire-ant immunotherapy prescriptions represented 45.9% of individual Hymenoptera immunotherapy prescriptions. The selected mastocytosis cohort included 14/97 persons with fire-ant-anaphylaxis history; 14/43 among participants who had experienced any anaphylaxis. (mcmurray2025fireantvenomanaphylaxis pages 1-2, mcmurray2025fireantvenomanaphylaxis pages 5-7, mcmurray2025fireantvenomanaphylaxis pages 7-9, mcmurray2025fireantvenomanaphylaxis pages 9-10)

The China compilation counted 8,749 selected, documented cases from 2004–2024, and modeled about 699,224 stung people annually, 8,181 with shock and 209 deaths; these modeled totals must not be reported as observed surveillance counts or reliable national incidence. The paper's body estimates 52,600 systemic-allergy presentations annually (7.52% of approximately 699,224): its abstract incorrectly prints 526,000, an approximately tenfold discrepancy. Its 120-million-person figure describes a broad population potentially threatened by invasion, not the denominator for the modeled annual sting estimate. Sex ratio, age-specific annual incidence and reliable global fire-ant-attributable mortality are not established by these datasets. Geographic exposure differs sharply: U.S. colonized states, mainland China, South America and recently established S. invicta in Sicily require separate interpretation. Inheritance, penetrance, carrier frequency, consanguinity and founder effects are not applicable to the injury itself. (chen2026analysisofthe pages 1-2, chen2026analysisofthe pages 2-4, mcmurray2025fireantvenomanaphylaxis pages 7-9, chen2026analysisofthe pages 6-8, dioguardi2024therapeuticpotentialof pages 2-4)

10. Diagnostics and differential diagnosis

Acute diagnosis is clinical: document the observed insect or mound, time and number of stings, stereotypical lesions, vital signs, respiratory symptoms and evidence of more than one organ system becoming involved. Treat suspected anaphylaxis on clinical grounds rather than waiting for test results. Following recovery from a systemic reaction, an allergist can correlate the history with fire-ant whole-body-extract skin-prick/intradermal tests and/or Solenopsis-specific serum IgE; an isolated positive sensitization test is not proof that the ant caused a past episode. In the Brazilian 33-patient study, entry required positive skin testing and positive ImmunoCAP i70 specific IgE. That report recommends waiting approximately 3–4 weeks after the event for allergy testing to reduce false negatives and measured basal tryptase as part of its assessment. Tryptase assists assessment of mast-cell disease but did not predict reaction grade in that selected cohort; two patients had values exceeding 11.4 µg/mL and systemic mastocytosis was ruled out. (watanabe2022clinicalandlaboratory pages 1-4, watanabe2022clinicalandlaboratory pages 4-7)

Consider other ant species, bees or wasps, nonvenomous insect bites, nonallergic local infection, cellulitis and alternative causes of sudden hypotension. A typical sterile pustule should not automatically be labeled bacterial infection. ECG, imaging, biopsy, renal testing or creatine kinase are indication-driven, not universal diagnostic requirements; consider renal/muscle testing after heavy stinging or suggestive symptoms. There is no established asymptomatic population, newborn, prenatal, carrier, WGS/WES, gene-panel, chromosomal-microarray, FISH, liquid-biopsy or omics screening test for fire-ant poisoning. For a concerning severe reaction, evaluation for an underlying clonal mast-cell disorder is distinct from diagnosing the sting itself. (chen2026analysisofthe pages 1-2, sukprasert2012characterizationofthe pages 1-3, mcmurray2025fireantvenomanaphylaxis pages 7-9, guillet2022partiinsect pages 4-5)

11. Outcomes and prognosis

Most local effects resolve without permanent injury, but a single systemic reaction can be life-threatening; heavy exposure may cause systemic complications. In the selected mast-cell-disease cohort, 20 fire-ant-anaphylaxis episodes included 11 grade III and nine grade II episodes; almost half initially went unrecognized as anaphylaxis or without epinephrine. These numbers describe severity in a high-risk referral cohort, not the prognosis after an arbitrary sting. In the China mixed-source series three of 8,749 reported cases died; this is a selected-case proportion and cannot be converted to a population case-fatality estimate. No defensible fire-ant-poisoning-specific five- or ten-year survival, life expectancy decrement, standardized disability score, or validated molecular prognostic marker was retrieved. Prognosis depends importantly on exposure burden, prompt treatment of systemic symptoms and host mast-cell disease; ocular injury and secondary infection can complicate recovery. (mcmurray2025fireantvenomanaphylaxis pages 7-9, mcmurray2025fireantvenomanaphylaxis pages 9-10, dioguardi2024therapeuticpotentialof pages 4-6, chen2026analysisofthe pages 6-8)

12. Treatment and real-world implementation

Immediate algorithm: remove the patient from the ants and assess airway, breathing, circulation and generalized symptoms. Suspected anaphylaxis warrants prompt intramuscular epinephrine and emergency services; airway/oxygen, positioning, intravenous fluids and repeated clinician-directed epinephrine as needed are supportive measures. Antihistamines or corticosteroids must not replace epinephrine for anaphylaxis. For uncomplicated local symptoms, cleanse the area and use cold compresses, analgesia and, as appropriate, a topical corticosteroid or antihistamine for itch; monitor for progressive swelling or infection. This combines fire-ant clinical literature with general sting/anaphylaxis management rather than claiming a fire-ant-specific randomized comparison of every supportive measure. Proposed NCIT intervention labels—epinephrine administration, antihistamine therapy, topical corticosteroid therapy, supportive care and allergen immunotherapy—require accession verification. (sukprasert2012characterizationofthe pages 1-3, rodrigo2018immunotherapyinanaphylaxis pages 5-6, rodrigo2018immunotherapyinanaphylaxis pages 4-5, shridhar2022insecttoxicityin pages 4-5, bowles2006fieldguideto pages 48-52)

Future-exposure prevention in allergic patients: Specialist-administered imported-fire-ant whole-body-extract subcutaneous immunotherapy is used following systemic sting allergy with convincing sensitization. This is a real-world service in U.S. TRICARE and was studied in Brazil with an S. invicta/S. richteri extract, escalating to 0.5 mL of 1:100 wt/vol maintenance. In the Brazilian study, 20 patients sustained 35 accidental stings during treatment; three had urticaria only. There were two mild build-up systemic treatment reactions, none during maintenance, and the fire-ant-specific IgG4/IgE ratio rose. The observed field-sting outcomes support effectiveness but are not a placebo-controlled prevention percentage; this cohort was small, selected for severe prior allergy and did not deliberately challenge all participants. Local injection reactions and occasional systemic immunotherapy reactions remain possible. The 2023 review identifies ongoing work on personalized venom-immunotherapy risk assessment and accelerated schedules; a distinct 2024 imported-fire-ant immunotherapy review is indexed but its full text was unavailable for verification here. (watanabe2022clinicalandlaboratory pages 10-13, watanabe2022clinicalandlaboratory pages 1-4, floyd2023updatesandrecent pages 15-17, mcmurray2025fireantvenomanaphylaxis pages 1-2)

Experimental registry finding: ClinicalTrials.gov NCT00435552 describes a completed, double-masked phase-1 evaluation of an Ease-it Spray procedure for sting pain; the retrieved registry record supplies no efficacy result. It is not a trial demonstrating treatment of anaphylaxis. No validated fire-ant-specific antivenom, gene/cell/RNA therapy, surgical correction, genotype-guided medication, or established human therapeutic use of solenopsin was found. Anti-inflammatory/anticancer applications of isolated venom components remain predominantly preclinical and must not be conflated with treating venom poisoning. (NCT00435552 chunk 1, dioguardi2024therapeuticpotentialof pages 6-8)

13. Prevention

Primary: Avoid disturbing mounds, implement surveillance and professionally appropriate colony control in inhabited areas, protect workers and other people with recurrent outdoor exposure, and provide locally relevant education about recognizing ants and nests. Secondary: Identify anaphylaxis immediately, administer epinephrine, and refer survivors of systemic reactions for allergy evaluation; there is no population screening program for asymptomatic people. Tertiary: Provide an individual emergency plan, prescribed autoinjector when indicated, and specialist discussion of whole-body-extract immunotherapy to prevent severe responses to later stings. There is no licensed vaccine, no established prophylactic drug for the general population and no indication for genetic carrier or prenatal screening. (chen2026analysisofthe pages 2-4, mcmurray2025fireantvenomanaphylaxis pages 9-10, rodrigo2018immunotherapyinanaphylaxis pages 5-6, rodrigo2018immunotherapyinanaphylaxis pages 4-5)

14. Other species and naturally occurring disease

Homo sapiens is the subject of the human clinical data; S. invicta, S. richteri and S. geminata are venom-producing exposure species, not human-to-human-transmitted infectious agents. Fire ants can also sting livestock and companion/wild animals: a 2024 review reports that newborn, sick or weakened farm animals may suffer severe attacks, eye injury or disrupted feeding. This establishes veterinary relevance but does not supply validated breed-specific incidence or companion-animal fire-ant case-fatality rates. No zoonotic transmission cycle is involved; cross-species susceptibility reflects exposure to the same venom. NCBI Taxon, VBO and ortholog accessions were not independently checked, and no breed or orthologous causal human gene should be assigned on present evidence. (dioguardi2024therapeuticpotentialof pages 2-4, shridhar2022insecttoxicityin pages 4-5)

15. Model organisms and experimental systems

The most directly relevant induced model is male BALB/c Mus musculus, aged 8–12 weeks in the 2018 original experiment. Hind-footpad sensitization with 10 or 100 µg of fire-ant venom protein and challenge 14 days later reproduced swelling and a type-2 inflammatory component; a separate ovalbumin co-sensitization experiment showed protein-extract adjuvanticity and loss of that effect after heat treatment. This model is useful for venom-protein allergen biology and candidate prevention mechanisms but does not reproduce an unmanipulated human sting, the alkaloid-rich venom dose, a proven human anaphylaxis incidence or decades-long clinical outcomes. A separate S. geminata study generated anti-Sol-gem-2 antibody in mice and tested venom neutralization using crickets; its insect paralysis endpoint is not a human anaphylaxis model. No validated disease-specific knockout, knock-in, humanized model, organoid, single-cell atlas or MGI accession was established. (zamithmiranda2018theallergicresponse pages 6-7, daniel2018theallergicresponse pages 6-9, zamithmiranda2018theallergicresponse pages 7-8, sukprasert2012characterizationofthe pages 1-3)

Primary-source quotations and publication links

  • Human epidemiology, 31 March 2025: McMurray et al., Frontiers in Allergy, doi:10.3389/falgy.2025.1570123, abstract: “Fire ant and flying Hymenoptera-venom anaphylaxis prevalence in the general population was 0.048% and 0.083%, respectively.” This is an administrative-population estimate, not a sting incidence estimate. (mcmurray2025fireantvenomanaphylaxis pages 1-2)
  • Human immunotherapy, published 5 March 2022: Watanabe et al., SN Comprehensive Clinical Medicine, doi:10.1007/s42399-022-01150-z; the accessible author preprint is doi:10.21203/rs.3.rs-909581/v1. Its abstract states: “Twenty patients had accidental stings during immunotherapy, with 3 presenting only urticaria.” Reported findings above were checked against that preprint, not independently against the journal's final text. (watanabe2022clinicalandlaboratory pages 1-4, watanabe2022clinicalandlaboratory pages 10-13)
  • Animal mechanism, September 2018: Zamith-Miranda et al., Scientific Reports, doi:10.1038/s41598-018-32327-z, abstract: “fire ant proteins per se can lead to an allergic response.” This is an experimental mouse finding. (zamithmiranda2018theallergicresponse pages 1-2, zamithmiranda2018theallergicresponse pages 7-8)
  • Human case compilation, 16 June 2026: Chen et al., PLOS ONE, doi:10.1371/journal.pone.0350501. The abstract states that symptoms were analyzed using “8,749 representative cases with detailed symptom descriptions”; the mixed-source ascertainment and abstract's systemic-allergy projection error require the qualifications given above. (chen2026analysisofthe pages 1-2, chen2026analysisofthe pages 2-4, chen2026analysisofthe pages 6-8)
  • Recent contextual review, November 2024: Dioguardi et al., Biomolecules, doi:10.3390/biom14121499, distinguishes bioactive venom constituents and preclinical drug discovery from demonstrated treatments for sting victims. Clinical use of venom alkaloids has not been established. (dioguardi2024therapeuticpotentialof pages 6-8, dioguardi2024therapeuticpotentialof pages 4-6)

Curation priority: Index this as an environmental envenomation/injury with separately annotated direct alkaloid toxicity, IgE-mediated systemic allergy and massive-sting complications. Preserve study-specific denominators and evidence types. Verify MONDO, HPO, GO, CL, UBERON, ChEBI, NCIT, taxon, ICD and PMID accessions against their source registries before entering exact database identifiers; none should be inferred merely from a plausible label. (NCT00435552 chunk 1, mcmurray2025fireantvenomanaphylaxis pages 5-7, sukprasert2012characterizationofthe pages 1-3, chen2026analysisofthe pages 6-8)

References

  1. (mcmurray2025fireantvenomanaphylaxis pages 2-3): Jeremy C. McMurray, Brandon J. Schornack, Karla E. Adams, Robert L. McCoy, Amanda K. Marshall, Janet A. Brunader, Irina Maric, Dean D. Metcalfe, and Nathan A. Boggs. Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis. Frontiers in Allergy, Mar 2025. URL: https://doi.org/10.3389/falgy.2025.1570123, doi:10.3389/falgy.2025.1570123. This article has 3 citations and is from a peer-reviewed journal.

  2. (sukprasert2012characterizationofthe pages 1-3): Sophida Sukprasert, N. Uawonggul, T. Jamjanya, S. Thammasirirak, Jureerut Daduang, and S. Daduang. Characterization of the allergen sol gem 2 from the fire ant venom, solenopsis geminata. Journal of Venomous Animals and Toxins Including Tropical Diseases, 18:325-334, Jan 2012. URL: https://doi.org/10.1590/s1678-91992012000300010, doi:10.1590/s1678-91992012000300010. This article has 18 citations and is from a peer-reviewed journal.

  3. (dioguardi2024therapeuticpotentialof pages 4-6): Mario Dioguardi, Stefania Cantore, Diego Sovereto, Lorenzo Sanesi, Angelo Martella, Lynn Almasri, Gennaro Musella, Lorenzo Lo Muzio, and Andrea Ballini. Therapeutic potential of solenopsis invicta venom: a scoping review of its bioactive molecules, biological aspects, and health applications. Biomolecules, 14:1499, Nov 2024. URL: https://doi.org/10.3390/biom14121499, doi:10.3390/biom14121499. This article has 9 citations.

  4. (dioguardi2024therapeuticpotentialof pages 2-4): Mario Dioguardi, Stefania Cantore, Diego Sovereto, Lorenzo Sanesi, Angelo Martella, Lynn Almasri, Gennaro Musella, Lorenzo Lo Muzio, and Andrea Ballini. Therapeutic potential of solenopsis invicta venom: a scoping review of its bioactive molecules, biological aspects, and health applications. Biomolecules, 14:1499, Nov 2024. URL: https://doi.org/10.3390/biom14121499, doi:10.3390/biom14121499. This article has 9 citations.

  5. (rodrigo2018immunotherapyinanaphylaxis pages 1-2): Collado Chagoya Rodrigo. Immunotherapy in anaphylaxis by tropical fire ant sting: a case report and literature review. ArXiv, 1:1-6, May 2018. URL: https://doi.org/10.31531/2581-5563.1000105, doi:10.31531/2581-5563.1000105. This article has 1 citations.

  6. (NCT00435552 chunk 1): Ease-it Spray for the Treatment of Fire Ant Stings. C.R.Darnall Army Medical Center. 2007. ClinicalTrials.gov Identifier: NCT00435552

  7. (mcmurray2025fireantvenomanaphylaxis pages 5-7): Jeremy C. McMurray, Brandon J. Schornack, Karla E. Adams, Robert L. McCoy, Amanda K. Marshall, Janet A. Brunader, Irina Maric, Dean D. Metcalfe, and Nathan A. Boggs. Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis. Frontiers in Allergy, Mar 2025. URL: https://doi.org/10.3389/falgy.2025.1570123, doi:10.3389/falgy.2025.1570123. This article has 3 citations and is from a peer-reviewed journal.

  8. (mcmurray2025fireantvenomanaphylaxis pages 1-2): Jeremy C. McMurray, Brandon J. Schornack, Karla E. Adams, Robert L. McCoy, Amanda K. Marshall, Janet A. Brunader, Irina Maric, Dean D. Metcalfe, and Nathan A. Boggs. Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis. Frontiers in Allergy, Mar 2025. URL: https://doi.org/10.3389/falgy.2025.1570123, doi:10.3389/falgy.2025.1570123. This article has 3 citations and is from a peer-reviewed journal.

  9. (watanabe2022clinicalandlaboratory pages 1-4): Alexandra Sayuri Watanabe, Marcelo Alves Ferreira, Anne Karoline Rocha Medrado Ventura, Clóvis Eduardo Santos Galvão, Jorge Kalil, Keity Souza Santos, and Fabio Fernandes Morato Castro. Clinical and laboratory profile of patients with anaphylaxis to fire ant venom (solenopsis sp) under specific subcutaneous immunotherapy. Unknown journal, Jan 2022. URL: https://doi.org/10.21203/rs.3.rs-909581/v1, doi:10.21203/rs.3.rs-909581/v1.

  10. (chen2026analysisofthe pages 2-4): Huimei Chen, Hong-Zhi Zhuang, Xiaojing Zhang, Yu-Ling Liang, Mingrong Liang, Yong-Yue Lu, and Lei Wang. Analysis of the human health threat caused by the red imported fire ant in mainland china. PLOS One, 21:e0350501, Jun 2026. URL: https://doi.org/10.1371/journal.pone.0350501, doi:10.1371/journal.pone.0350501. This article has 1 citations and is from a peer-reviewed journal.

  11. (mcmurray2025fireantvenomanaphylaxis pages 7-9): Jeremy C. McMurray, Brandon J. Schornack, Karla E. Adams, Robert L. McCoy, Amanda K. Marshall, Janet A. Brunader, Irina Maric, Dean D. Metcalfe, and Nathan A. Boggs. Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis. Frontiers in Allergy, Mar 2025. URL: https://doi.org/10.3389/falgy.2025.1570123, doi:10.3389/falgy.2025.1570123. This article has 3 citations and is from a peer-reviewed journal.

  12. (mcmurray2025fireantvenomanaphylaxis pages 9-10): Jeremy C. McMurray, Brandon J. Schornack, Karla E. Adams, Robert L. McCoy, Amanda K. Marshall, Janet A. Brunader, Irina Maric, Dean D. Metcalfe, and Nathan A. Boggs. Fire ant-venom anaphylaxis prevalence in the general population and patients with systemic mastocytosis. Frontiers in Allergy, Mar 2025. URL: https://doi.org/10.3389/falgy.2025.1570123, doi:10.3389/falgy.2025.1570123. This article has 3 citations and is from a peer-reviewed journal.

  13. (rodrigo2018immunotherapyinanaphylaxis pages 4-5): Collado Chagoya Rodrigo. Immunotherapy in anaphylaxis by tropical fire ant sting: a case report and literature review. ArXiv, 1:1-6, May 2018. URL: https://doi.org/10.31531/2581-5563.1000105, doi:10.31531/2581-5563.1000105. This article has 1 citations.

  14. (guillet2022partiinsect pages 3-4): Carole Guillet, Oliver Yves Martin, Cordula Meincke, Lukas Joerg, and Peter Schmid-Grendelmeier. Part i: insect stings and bites—beyond the realm of bee and wasp allergies. Allergo Journal International, 31:183-193, Feb 2022. URL: https://doi.org/10.1007/s40629-022-00199-5, doi:10.1007/s40629-022-00199-5. This article has 9 citations and is from a peer-reviewed journal.

  15. (chen2026analysisofthe pages 1-2): Huimei Chen, Hong-Zhi Zhuang, Xiaojing Zhang, Yu-Ling Liang, Mingrong Liang, Yong-Yue Lu, and Lei Wang. Analysis of the human health threat caused by the red imported fire ant in mainland china. PLOS One, 21:e0350501, Jun 2026. URL: https://doi.org/10.1371/journal.pone.0350501, doi:10.1371/journal.pone.0350501. This article has 1 citations and is from a peer-reviewed journal.

  16. (chen2026analysisofthe pages 6-8): Huimei Chen, Hong-Zhi Zhuang, Xiaojing Zhang, Yu-Ling Liang, Mingrong Liang, Yong-Yue Lu, and Lei Wang. Analysis of the human health threat caused by the red imported fire ant in mainland china. PLOS One, 21:e0350501, Jun 2026. URL: https://doi.org/10.1371/journal.pone.0350501, doi:10.1371/journal.pone.0350501. This article has 1 citations and is from a peer-reviewed journal.

  17. (chen2026analysisofthe media 303ec5e0): Huimei Chen, Hong-Zhi Zhuang, Xiaojing Zhang, Yu-Ling Liang, Mingrong Liang, Yong-Yue Lu, and Lei Wang. Analysis of the human health threat caused by the red imported fire ant in mainland china. PLOS One, 21:e0350501, Jun 2026. URL: https://doi.org/10.1371/journal.pone.0350501, doi:10.1371/journal.pone.0350501. This article has 1 citations and is from a peer-reviewed journal.

  18. (zamithmiranda2018theallergicresponse pages 6-7): Daniel Zamith-Miranda, Eduardo G. P. Fox, Ana Paula Monteiro, Diogo Gama, Luiz E. Poublan, Almair Ferreira de Araujo, Maria F. C. Araujo, Georgia C. Atella, Ednildo A. Machado, and Bruno L. Diaz. The allergic response mediated by fire ant venom proteins. Scientific Reports, Sep 2018. URL: https://doi.org/10.1038/s41598-018-32327-z, doi:10.1038/s41598-018-32327-z. This article has 22 citations and is from a peer-reviewed journal.

  19. (zamithmiranda2018theallergicresponse pages 1-2): Daniel Zamith-Miranda, Eduardo G. P. Fox, Ana Paula Monteiro, Diogo Gama, Luiz E. Poublan, Almair Ferreira de Araujo, Maria F. C. Araujo, Georgia C. Atella, Ednildo A. Machado, and Bruno L. Diaz. The allergic response mediated by fire ant venom proteins. Scientific Reports, Sep 2018. URL: https://doi.org/10.1038/s41598-018-32327-z, doi:10.1038/s41598-018-32327-z. This article has 22 citations and is from a peer-reviewed journal.

  20. (daniel2018theallergicresponse pages 6-9): Zamith-Miranda Daniel, Eduardo G. P. Fox, Ana Paula Monteiro, Diogo Gama, Luiz E. Poublan, Almair Ferreira de Araujo, Maria F. C. Araujo, Georgia C. Atella, Ednildo A. Machado, and Bruno L. Diaz. The allergic response mediated by fire ant venom proteins. Scientific Reports, Aug 2018. URL: https://doi.org/10.1101/382697, doi:10.1101/382697. This article has 16 citations and is from a peer-reviewed journal.

  21. (zamithmiranda2018theallergicresponse pages 7-8): Daniel Zamith-Miranda, Eduardo G. P. Fox, Ana Paula Monteiro, Diogo Gama, Luiz E. Poublan, Almair Ferreira de Araujo, Maria F. C. Araujo, Georgia C. Atella, Ednildo A. Machado, and Bruno L. Diaz. The allergic response mediated by fire ant venom proteins. Scientific Reports, Sep 2018. URL: https://doi.org/10.1038/s41598-018-32327-z, doi:10.1038/s41598-018-32327-z. This article has 22 citations and is from a peer-reviewed journal.

  22. (dioguardi2024therapeuticpotentialof pages 6-8): Mario Dioguardi, Stefania Cantore, Diego Sovereto, Lorenzo Sanesi, Angelo Martella, Lynn Almasri, Gennaro Musella, Lorenzo Lo Muzio, and Andrea Ballini. Therapeutic potential of solenopsis invicta venom: a scoping review of its bioactive molecules, biological aspects, and health applications. Biomolecules, 14:1499, Nov 2024. URL: https://doi.org/10.3390/biom14121499, doi:10.3390/biom14121499. This article has 9 citations.

  23. (watanabe2022clinicalandlaboratory pages 13-16): Alexandra Sayuri Watanabe, Marcelo Alves Ferreira, Anne Karoline Rocha Medrado Ventura, Clóvis Eduardo Santos Galvão, Jorge Kalil, Keity Souza Santos, and Fabio Fernandes Morato Castro. Clinical and laboratory profile of patients with anaphylaxis to fire ant venom (solenopsis sp) under specific subcutaneous immunotherapy. Unknown journal, Jan 2022. URL: https://doi.org/10.21203/rs.3.rs-909581/v1, doi:10.21203/rs.3.rs-909581/v1.

  24. (watanabe2022clinicalandlaboratory pages 4-7): Alexandra Sayuri Watanabe, Marcelo Alves Ferreira, Anne Karoline Rocha Medrado Ventura, Clóvis Eduardo Santos Galvão, Jorge Kalil, Keity Souza Santos, and Fabio Fernandes Morato Castro. Clinical and laboratory profile of patients with anaphylaxis to fire ant venom (solenopsis sp) under specific subcutaneous immunotherapy. Unknown journal, Jan 2022. URL: https://doi.org/10.21203/rs.3.rs-909581/v1, doi:10.21203/rs.3.rs-909581/v1.

  25. (guillet2022partiinsect pages 4-5): Carole Guillet, Oliver Yves Martin, Cordula Meincke, Lukas Joerg, and Peter Schmid-Grendelmeier. Part i: insect stings and bites—beyond the realm of bee and wasp allergies. Allergo Journal International, 31:183-193, Feb 2022. URL: https://doi.org/10.1007/s40629-022-00199-5, doi:10.1007/s40629-022-00199-5. This article has 9 citations and is from a peer-reviewed journal.

  26. (rodrigo2018immunotherapyinanaphylaxis pages 5-6): Collado Chagoya Rodrigo. Immunotherapy in anaphylaxis by tropical fire ant sting: a case report and literature review. ArXiv, 1:1-6, May 2018. URL: https://doi.org/10.31531/2581-5563.1000105, doi:10.31531/2581-5563.1000105. This article has 1 citations.

  27. (shridhar2022insecttoxicityin pages 4-5): NB Shridhar. Insect toxicity in domestic animals. Unknown journal, 2022.

  28. (bowles2006fieldguideto pages 48-52): DE Bowles and JA Swaby. Field guide to venomous and medically important invertebrates affecting military operations: identification, biology, symptoms, treatment. Unknown journal, 2006.

  29. (watanabe2022clinicalandlaboratory pages 10-13): Alexandra Sayuri Watanabe, Marcelo Alves Ferreira, Anne Karoline Rocha Medrado Ventura, Clóvis Eduardo Santos Galvão, Jorge Kalil, Keity Souza Santos, and Fabio Fernandes Morato Castro. Clinical and laboratory profile of patients with anaphylaxis to fire ant venom (solenopsis sp) under specific subcutaneous immunotherapy. Unknown journal, Jan 2022. URL: https://doi.org/10.21203/rs.3.rs-909581/v1, doi:10.21203/rs.3.rs-909581/v1.

  30. (floyd2023updatesandrecent pages 15-17): Michelle L. Floyd, Karla E. Adams, and David B. K. Golden. Updates and recent advances on venom immunotherapy. Current Treatment Options in Allergy, 10:1-19, Apr 2023. URL: https://doi.org/10.1007/s40521-023-00336-7, doi:10.1007/s40521-023-00336-7. This article has 30 citations and is from a peer-reviewed journal.

Artifacts

Reference Validation

Checked with linkml-reference-validator 0.3.0.

Outcome Count
References checked 11
Resolved 11
Unresolved (possible confabulation) 0
Unverifiable 0
References weighed for topical relevance 11
On topic 4
Off topic 0

All extracted references resolved successfully.

Term Validation

Checked with linkml-term-validator 0.4.5, through the ols: adapter.

Outcome Count
Terms checked 1
Resolved 1
Unresolved (possible confabulation) 0
Obsolete 0
Unverifiable 0
Terms whose name was checked 1
Terms named correctly 0
Terms named as a different term 0
Terms whose name is worth a second look 1

Terms whose name is worth a second look

The report's name for these is recognisably related to the term's own name without being one of them. A loose paraphrase reads the same way as a citation of the wrong sibling term - and so does a related synonym, which the ontology records precisely because it names something adjacent rather than the same thing - so these are listed rather than judged:

  • MONDO:0100341 (2 mentions) - the report calls it "if available"; MONDO calls it fire ant poisoning, and lists "fire ant allergy" among its other names

Every term resolved, and every label the report gave matched.