Ant allergens and hypersensitivity reactions in response to ant stings

 Review article
Ant allergens and hypersensitivity reactions in response
to ant stings
Rutcharin Potiwat1 and Raweerat Sitcharungsi2
Summary
Hypersensitivity reactions caused by ant
stings are increasingly recognized as an important
cause of death by anaphylaxis. Only some species
of ants ( e.g. Solenopsis spp., Myrmecia spp., and
Pachycondyla spp.) cause allergic reactions. Ant
species are identified by evaluating the morphologic
structures of worker ants or by molecular
techniques. Ant venom contains substances,
including acids and alkaloids, that cause toxic
reactions, and those from Solenopsis invicta or
the imported fire ant have been widely studied.
Piperidine alkaloids and low protein contents can
cause local reactions (sterile pustules) and
systemic reactions (anaphylaxis). Imported fire
ant venoms are cross-reactive; for example, the
Sol i 1 allergen from S. invicta has crossreactivity with yellow jacket phospholipase. The
Sol i 3 allergen is a member of the antigen 5
family that has amino acid sequence identity with
vespid antigen 5. The clinical presentations of ant
hypersensitivity are categorized into immediate
and delayed reactions: immediate reactions, such
as small local reactions, large local reactions, and
systemic reactions, occur within 1–4 hours after
the ant stings, whereas delayed reactions, such as
serum sickness and vasculitis, usually occur more
than 4 hours after the stings. Tools for the
diagnosis of ant hypersensitivity are skin testing,
serum specific IgE, and sting challenge tests.
Management of ant hypersensitivity can be
divided into immediate (epinephrine, corticosteroids),
symptomatic (antihistamines, bronchodilators),
supportive (fluid resuscitation, oxygen therapy),
and preventive (re-sting avoidance and
immunotherapy) treatments. (Asian Pac J Allergy
Immunol 2015;33:267-75)
From 1. Department of Medical Entomology, Faculty of
Tropical Medicine, Mahidol University, Bangkok, Thailand
2. Department of Tropical Pediatrics, Faculty of Tropical
Medicine, Mahidol University, Bangkok, Thailand
Corresponding author: Raweerat Sitcharungsi
E-mail: [email protected]
Submitted date: 11/12/2015
Keywords: Allergy, ant stings, hypersensitivity,
immunotherapy, treatment
Introduction
Ants are insects and belong to the order
Hymenoptera and the family Formicidae. There are
currently more than 12,500 ant species known.
Although some species of ants can bite and sting
humans, only some ant genera, such as Solenopsis,
especially S. invicta and S. ricteri (commonly known as
imported fire ants), cause life-threatening allergic
reactions. Ant hypersensitivity is one of the most
important causes of severe systemic reactions or
anaphylaxis with reports of fatalities from ant
anaphylaxis occurring worldwide in both urban and
rural areas. The diagnosis of ant hypersensitivity can
be performed by allergic history and physical
examination of the ant sting, or by in vivo and in
vitro tests. The management of ant hypersensitivity
can be divided into immediate treatment for
anaphylaxis, and preventive treatment. However,
knowledge of ant-induced allergic reactions in some
parts of the world is limited. This article reviews ant
diversity and distribution, the medical importance of
ant stings, ant allergens, and their cross-reactivity, as
well as the clinical presentations and management of
ant hypersensitivity reactions. This information will
enhance the basic knowledge of ants for scientists
and provide an overview of therapeutic guidelines
for physicians.
Ant diversity and distribution
Ants are social insects classified in the family
Formicidae, order Hymenoptera. Ants are diversely
spread among continents and biogeographic regions
with more than 12,500 species in 290 genera
belonging to 21 subfamilies having been identified
thus far. Tropical areas and continental forests have
the greatest influence on the presence of ant species
diversity. In Thailand, 247 ant species distributed
among 55 genera in nine subfamilies have been
recorded.1-4 Six of these species (Aenictus artipus,
Leptanilla thai, Lophomyrmex striatulus, Tetramorium
ciliatum, Tetramorium flavipes, and Tetraponera
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Asian Pac J Allergy Immunol 2015;33:267-75
notabilis) were originally described from Thai territories
and are located in agricultural fields and forests.5
Invasive ants are exotic species that establish
colonies outside their native areas and can cause a
decline or a change in diversity, community, and
populations of native invertebrates, vertebrates, and
plants by their invasion and displacement.6
However, invasive ant species, such as Solenopsis
geminata and Tetraponera rufonigra, can also play
an important role in the impact on clinical
hypersensitivity reaction.7, 8 The important invasive
ant species are widely distributed worldwide (Table
1).9-11 Of these invasive ant species, Anoplolepis
gracilipes (yellow crazy ant), Pheidole megacephala
(big-headed ant), and Solenopsis geminata (tropical
fire ant) are all present in Thailand.6 The yellow
crazy ant is thought to decrease the diversity and
population of native fauna and flora in ecosystems
due to its replacement of natural native species, but
information on its distribution is rarely reported.
The medical importance of ant-induced hypersensitivity
Thailand has a number of ants of medical
importance. The red imported fire ant (Solenopsis
invicta, Buren) is an important invasive ant species
that is also present in many other parts of the world,
and is considered to cause hypersensitivity in both
children and adults. Other fire ants in the genus
Solenopsis, including S. invicta, S. richteri, S.
geminata, S. saevissima, S. xyloni, and S. aurea can
cause allergic reactions.10, 12 Importantly, there is
cross-reactivity among venoms of the Solenopsis
species, such as S. xyloni and S. aurea, and other
hymenoptera.13, 14 The tropical fire ant (S. geminata)
is a natural native species with a wide distribution
throughout Thailand whose stings can cause allergic
reactions. Another group of ants that cause
hypersensitivity belong to the genus Myrmecia,
especially M. pilosula, which are found in
Australia.15-17 However, the ant species that are most
commonly responsible for anaphylaxis in Thai
patients are Solenopsis geminata, Tetraponera
rufonigra, and Odontoponera denticulata (Figure 1).
Patients with stings from these ants were referred to
tertiary
care
hospitals
in
Bangkok
for
immunotherapy, and ants were sent for species
identification at the Faculty of Tropical Medicine,
Mahidol University (unpublished data). All three
species are aggressive ants with painful bites or
stings. Both T. rufonigra and O. denticulata have a
stinger at the end of the gaster (Figure 2). T.
rufonigra-induced hypersensitivity has been
reported in humans after stings and can cause severe
anaphylaxis.18 The first case of T. rufonigra-induced
anaphylaxis was reported from Thailand. The patient
was a 17-month-old girl who presented with two
episodes of urticaria, angioedema, dyspnea, and loss
of consciousness.7
Species identification of the most common causative
species of ant anaphylaxis in Thailand
The most common causative species of ant
anaphylaxis in Thai patients are Solenopsis geminata,
Tetraponera rufonigra, and Odontoponera denticulata.
S. geminata belongs to the family Formicidae,
subfamily Myrmicinae, genus Solenopsis, species
geminata. The morphology of Solenopsis can be
confused with a smaller species of Monomorium,
although Solenopsis is distinguished by the presence
of a two-segmented petiole.19, 20 Identification of fire
ant species is very difficult and involves evaluating
the morphology of worker ants rather than just one
specimen. S. geminata workers have a polymorphic
size of 3–8 mm body length. The body has a reddish
brown color and is mostly smooth and shiny,
without sculpture. The head of the S. geminata
worker is divided into two notches, while in S.
invicta workers these notches are absent (Figure 2).
The differentiation of tropical fire ant morphology is
determined using worker ants but can also be
characterized using molecular techniques based on
mitochondrial DNA encoding cytochrome oxidase
subunit I (COI) or the internally-transcribed spacer
(ITS) gene.21 The differentiation of Solenopsis species
by morphology alone is difficult and can often be
confused with other species; therefore, molecular
identification is now widely used. PCR
amplification of the COI gene followed by cutting
nucleotide sequences with the HinfI restriction
enzyme can be used to distinguish S. invicta, S.
geminata, and S. xyloni from Florida.22 However,
even though molecular amplification is now widely
used, it is expensive.
T. rufonigra belongs to the family Formicidae,
subfamily Ponerinae, genus Tetraponera, species
rufonigra. It is black and shiny except on their
alitrunk that has an orange line, which is the specific
characteristic of T. rufonigra. Differentiation of
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Hypersensitivity to ant stings Table 1. The geographical distribution of major invasive ant species.
Ant species
Geographical Range
Reference(s)
Native
Invasive species
Anoplolepis gracilipe*
Africa, Tropical
Africa, Asia, Australia, Caribbean, Indian and Pacific
(Yellow crazy ant)
Asia?
Ocean
91
Dinoponera gigantea
Amazonian states
92
Hypoponera sp.
Brazil, Malaysia
93, 94
95, 96
Linepithema humile
South America,
Africa, Asia, North America, Atlantic and Pacific
(Argentine ants)
Argentina
Ocean, North Carolina (US)
Myrmecia pilosula
Far East, Australia
47, 66, 71
Odontomachus bauri
Caracas, Venezuela
71, 97
Virginia, North and South Carolina (US), Georgia
98, 99
Pachycondyla chinensis (Chinese
Japan, Asia
needle ant)
Pachycondyla sennaarensis
(US)
West Africa
Australia, Iran, Saudi Arabia
100, 101
Africa
Australia, North and South America, Caribbean,
10
(Samsum ants)
Pheidole megacephala
(Big-headed ant)
Indian and Pacific Ocean
Pseudomyrmex ejectus
Brazil
71
Rhytidoponera metallica
Queensland (Australia)
71
Southern California (US)
13
Solenopsis geminata
Central, North
Asian islands including Indonesia, Taiwan, Pacific
44, 102-104
(Tropical fire ant)
and South
island, Florida, Hawaii, Caribbean, and Thailand
Solenopsis aurea
America, Asia
Solenopsis invicta
South America
(Red imported fire ant)
Solenopsis richteri
Spain, southern China, southeast Asia, Brisbane,
13, 105-107
Australia, North American western states, Brazil
South America
Saudi Arabia, Mississippi, Alabama, North America
13, 44, 108
(Black imported fire ant)
Solenopsis saevissima
São Paolo (Brazil)
109, 110
Solenopsis xyloni
Southwestern states (US), Mexico
13, 44
Sri Lanka, Thailand
7, 18
Wasmannia auropunctata
Central and South
Africa, Caribbean, Pacific Ocean, South and North
111, 112
(Little fire ant)
America
America
Tetraponera rufonigra
*
Origin of the yellow crazy ant is unknown although some studies indicate it is from tropical Asia.
T. rufonigra and O. denticulata can be done by the
body shape, color, and the number of nodes on the
petiole segments. T. rufonigra has two nodes on the
petiole segment while, O. denticulata has a single
node (Figure 1). Moreover, O. denticulata has a
narrow node with a small spine on the petiole
segment.
Ant sting and venom isolation
The tropical fire ant (S. geminata) is an
aggressive fire ant with a painful sting that is
potentially life threatening.23 Normally, anaphylactic
reactions caused by ants occur in patients that come
into contact with the ant venom during stinging.24 In
general, the constituents of ant venom responsible
for anaphylaxis are composed of spray acid and
alkaloids derived from piperidine.25,26 The ant
venom is usually injected from a poison gland
located at the posterior part of the ant (gaster),
which secretes various chemicals from different
compartments depending on whether the ant is a
queen or a worker.20 The main toxic chemicals from
an S. geminata queen were identified by gas
chromatography–mass spectrometry and included 2alkyl-6-methylpiperidine alkaloids, -lactone, and
-pyrone, which were originally identified as
components of the S. invicta queen attractant
pheromone.19
Ant whole body extract (WBE) or the induced
secretion of poison from the posterior gland has
been used for ant immunotherapy.27-29 This isolated
venom is collected by a micro-glass tube during
induced ant stinging,29, 30 and might be useful for
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Asian Pac J Allergy Immunol 2015;33:267-75
(A) Solenopsis geminata
(B) Tetraponera rufonigra
(C) Odontoponera denticulata
Figure 1. Species of ants most often responsible for anaphylaxis in Thai patients.
immunotherapy or testing the cross-reactivity to
other hymenoptera, although it is difficult to isolate
and the activity is easily lost.31, 32 Currently, S.
invicta WBE is commercially available for skin
testing.25, 33, 34
Ant allergens
Ant venoms are composed of various
biologically active peptides and protein components
with each ant species having a variety of major
allergenic proteins. The most frequently studied ant
venom components are from fire ants with the
venom of the red imported fire ant (S. invicta) being
the most extensively investigated.35 Each S. invicta
sting transfers 0.04 to 0.11 µL of venom and 10 to
100 ng of proteins.36 The alkaloid part of the S.
invicta venom causes a sterile pustule at the sting
site, and has cytotoxic and hemolytic properties.37
The protein part is composed of four major
allergens, i.e., Sol i 1, Sol i 2, Sol i 3, and Sol i 4.38
Sol i 1 is a 37-kDa protein with phospholipase A1
activity that comprises 2–5% of the total venom
protein.39 Sol i 2 is a 26-kDa protein that is also
present in the venom of other species but is
dissimilar to the other sol allergens. This allergen
comprises 67% of the total venom proteins. Sol i 3
is a 24-kDa protein that is a member of the antigen 5
family and comprises 20% of the total venom
protein. Sol i 4 has a 13-kDa molecular mass and
comprises 9% of the total venom proteins, which are
different from the other sol allergens.14
There are still limited data on protein allergens
from ants in Asia, especially those in Thailand
where T. rufonigra and S. geminata are the most
common causative species of ant anaphylaxis.8 T.
rufonigra protein allergen was characterized and
identified by immunoblot assay and showed a
dominant active protein of approximately 120 kDa.7
A study of S. geminata allergen revealed that it was
composed of four venom proteins: Sol gem 1, Sol
gem 2, Sol gem 3, and Sol gem4 with molecular
weights of 37, 28, 26, and 16 kDa, respectively.40 Of
these, Sol gem 2 has a dimer form with a molecular
weight of 28/15 kDa (under non-reducing and
reducing condition). The amino acid sequence
analysis of Sol gem 2 exhibited a degree of
homology with the Sol i 2 allergen of S. invicta and
their allergenic properties are probably similar. A
study of Myrmecia ant venom identified many
venom allergens with post-translational processing,
and found that most allergen activity was caused by
disulfide-linked heterodimers.41
Ant venom nomenclature
The International Union of Immunological
Studies Allergen Nomenclature Subcommittee
(IUIS) has assigned official names to fire ant
allergens based on venom proteins: 1 was assigned
to phospholipase A1B; 2 was assigned to Sol i 2
homologous proteins; 3 was assigned to antigen 5related proteins; and 4 was assigned to Sol i 4
homologous proteins.42 A revision of the nomenclature
of allergenic components of Myrmecia should be
done to conform to the IUIS guidelines.43
Cross-reactivity among Solenopsis species
In addition to S. invicta, four other species of
Solenopsis, including S. richteri (black imported fire
ant), S. xyloni (southern fire ant), S. aurea (desert
fire ant), and S. geminata (tropical fire ant) also
cause allergic reactions.44
Regarding the structure of S. richteri allergens,
Sol r 1 and Sol r 3 are similar to Sol i 1 and Sol i 3
allergens from S. invicta, respectively, while the Sol
r 2 allergen of S. richteri and S. invicta have less
homology.44 There is no allergen that is analogous to
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Hypersensitivity to ant stings Sol i 4 in S. richteri even though the venom
allergens of S. richteri and S. invicta appear to be
allergenically similar.45
A study of S. xyloni allergic reactions showed
that serum from patients with reactions to stings by
S. xyloni were reactive to Sol i 1 and Sol i 3, but
were only marginally reactive to Sol i 2.44
Allergic reactions from S. aurea stings are
reported occasionally, but data is limited.
Nonetheless, cross-reactivity between allergens of S.
aurea and S. invicta, especially Sol 1 and Sol 3,
have been reported.44
The structures of four S. geminata venom
proteins appear to be similar to the Sol i 1, Sol i 2,
Sol i 3, and Sol i 4 allergens of S. invicta. The Sol
gem 2 allergen from S. geminata venom was
characterized and shown to have allergenic
properties similar to those of Sol i 2 from S.
invicta.40 Sol i 2 has 72.3% amino acid sequence
homology with Sol gem 2 and 78.2% sequence
homology with Sol r 2.46 In summary, there are
some sequence differences between the Sol 2 and
Sol 4 antigens of all fire ant venoms, but IgE
antibodies against fire ant venoms are highly crossreactive. Indeed, reactions to stings from any fire ant
species can cause sensitization to other species.
Cross-reactivity between Solenopsis species and
other ants
Ants of the genus Pachycondyla are a major
cause of ant hypersensitivity in Asia and the Middle
East.47,48 Studies of cross-reactivity between
Pachycondyla and imported fire ants are
controversial, however. A study from Korea
revealed no cross-reactivity,49 but another study
from the Middle East showed cross-reactivity
between Pachycondyla sennaarensis and imported
fire ant venom by immunoblot testing.50
Ants of the genus Myrmecia are the
predominant cause of ant hypersensitivity in
Australia.51 Allergens from these ants are complex
with highly basic peptides.42, 52 However, no
evidence of cross-reactivity between Myrmecia and
fire ant venom was found in allergic patient sera.46
Figure 2. Morphological outline of the tropical imported fire ant (Solenopsis geminata). Tropical fire ant (S.
geminata) workers are usually used for species identification. S. geminata has the sting apparatus at the end of gaster
and the number of petiole segments is usually used for species identification.
(A) S. geminata workers have a 2-segmented petiole and two notches on the head.
(B) The ant body is divided into four parts including head, alitrunk, petiole, and gaster.
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Asian Pac J Allergy Immunol 2015;33:267-75
Cross-reactivity between Solenopsis species and
other hymenoptera
Cross-reactivity among insects and unique ant
allergens have been established for some
hymenoptera venoms with studies reporting crossreactivity among major proteins of vespids (yellow
jackets) and S. invicta. The Sol i 1 allergen of S.
invicta is a phospholipase related to those found in
vespid venom with 33–38% amino acid identity.39, 53
A study reported cross-reactivity between Sol i 1
and
vespid
phospholipase
with
clinical
significance.54 Sol i 3 is a member of the antigen 5
family with 43–50% amino acid sequence identity
with vespid antigen 5.14, 55, 56 Sol i 3, however, has
few conserved areas in common with vespid antigen
5, and there is a lack of IgE cross-reactivity between
the two allergens.56, 57
Clinical presentation of ant hypersensitivity
Hymenoptera sting-induced anaphylaxis has
been reported worldwide, as well as in Thailand,58
with studies revealing cases of ant-induced severe
hypersensitivity reactions.7, 59
Reactions to ant hypersensitivity can be divided
into immediate- and delayed-type hypersensitivity
reactions. Immediate reactions occur within 1–4
hours after ant stings, and can be further divided into
normal local reactions (pain, swelling, erythema,
heat, and sterile pustules at sting sites), large local
reactions (a reaction larger than 10 cm in diameter
persisting for longer than 24 hours), generalized
cutaneous reactions (pruritus and urticaria), and
systemic reactions (anaphylaxis).35
There have been many previous reports of
imported fire ant-induced hypersensitivity reactions
and anaphylaxis. A large study of 20,755 cases with
fire ant stings estimated that 413 patients (2%) had
anaphylaxis.60 Another study showed that S. invictainduced hypersensitivity reactions were the cause of
death in 83 of 29,300 patients in a physician
survey.61 Infants and elderly people are at risk of
indoor imported fire ant stings. A review of local
newspapers in the United States between 1991 and
2004 revealed 10 indoor fire ant stings that were
previously unreported and 10 stings that were
reported in the medical literature. Six of the 20
patients died within one week after hypersensitivity
reactions occurred.62
Immediate reactions from the stings of ants
other than imported fire ants have also been
reported. Ants of the genus Pachycondyla are the
most common cause of anaphylaxis in tropical areas
of Asia and the Middle East. Pachycondyla
sennaarensis was the cause of anaphylaxis in 31
United Arab Emirates patients with positive skin
tests and specific IgE antibodies to this ant,63 and
Pachycondyla chinensis induced large local
reactions after stings in 1.6% of patients in Korea.
Another study showed that 7 of 327 patients (2.1%)
had systemic immediate reactions and that four
patients had anaphylaxis.64 Ants of the genus
Myrmecia in Australia caused several deaths from
anaphylaxis.65,66 Fatal anaphylaxis from the southern
fire ant or S. xyloni in the United States was also
reported.67 Nonfatal immediate reactions from S.
xyloni were also shown in other studies.68, 44 Other
native fire ants (S. aurea and S. geminata) caused
immediate hypersensitivity reactions in studies from
the United States69, as did harvester ants (genus
Pogonomyrmex) and oak ants (Pseudomyrmex
species).70, 71 Delayed reactions usually occur more
than 4 hours after ant stings and cause dermatitis,
arthralgia, and lymphadenopathy from serum
sickness, renal abnormalities, and vasculitis,
respectively.72 Serum sickness from fire ant attacks
was reported in the United States73 and nephrotic
syndrome occurred in a child two weeks after being
stung by a fire ant.74
Diagnosis of ant-induced hypersensitivity
Diagnosis of ant-induced hypersensitivity can be
performed by documenting a patient history of
allergic reaction to ant stings, by physical
examination, or through the use of in vivo and/or in
vitro tests. A history of the circumstances of the
sting, including where it occurred, what the
individual was doing, and the nature of the ant
habitat, should be asked. Identification of the
causative ant should be determined by an
entomological specialist. Physical examination for
evidence of ant stings should also be completed.
Vital signs, as well as respiratory and
gastrointestinal signs and symptoms, should be
carefully examined for evidence of anaphylaxis.
Skin lesions, such as pseudopustules at the sting site
within 24 hours after being stung, can also help
diagnose imported fire ant stings.
A widely used in vivo method to diagnose fire
ant-sting hypersensitivity includes skin testing using
imported fire ant WBE. The result is positive when
the skin-prick test is performed using a
concentration of 1:1000 (w/v) of imported fire ant
WBE. If the skin-prick test result is negative, an
intradermal skin test using concentrations of
1:1,000,000 to 1:1000 (w/v) of the imported fire ant
WBE should be performed.75
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Hypersensitivity to ant stings Serum specific IgE to imported fire ant venom
can be used as an in vitro test to diagnose
hypersensitivity to imported fire ants. The
sensitivity of serum specific IgE is lower than skin
testing and therefore, is only recommended when
skin testing cannot be done or interpreted. Serum
specific IgE testing can also help in diagnosis of
imported fire ant allergy in suspected cases with
negative skin-test results.76 Twenty-nine percent of
adults with a history of fire ant exposure without
systemic reactions had a positive skin-test result.77 A
study revealed that 24% of non-allergic control
cases had positive specific-IgE test results for
imported fire ant venom.54 Skin testing and serum
specific IgE should not be performed without a
clinical history of allergic reactions from imported
fire ants because of the high degree of asymptomatic
IgE production in an exposed population.68, 78
The skin-prick test was used to diagnose P.
chinensis anaphylaxis in Korea and higher P.
chinensis-specific IgE levels were observed in
patients with anaphylaxis compared with patients
with large local reactions or the asymptomatic
population.48
The ant-sting challenge test is used for patients
with a history of ant anaphylaxis but negative skin
testing and serum specific IgE results. It has not
been used extensively because of the chance of
provoking serious allergic reactions. Specialized
centers are required for sting challenges.79, 80
Management of ant-induced hypersensitivity
Management of ant-induced hypersensitivity
can involve either immediate treatment for
anaphylaxis or preventive treatment. Immediate
treatment for anaphylaxis includes epinephrine at a
dosage of 0.01 mg/kg to a maximum of 0.3 mg for
children and 0.3 to 0.5 mg for adults.81, 82 An
epinephrine auto-injector should be prescribed for
patients with histories of severe allergic reactions.
Other medications, including antihistamines and
bronchodilators, should be given as symptomatic
treatments. Late-phase anaphylaxis can be prevented
by corticosteroids. Supportive treatments should
follow standard guidelines for anaphylaxis,
including fluid resuscitation, oxygen therapy, and
placing the individual in a recumbent position.82
Local reactions can be treated by local wound care,
including wound dressing, topical or systemic
antibiotics
for
secondary
infection,
cold
compression to reduce local swelling, and topical
corticosteroids to limit the swelling of large local
reactions. Pseudopustules from fire ant stings should
be kept clean and intact to prevent secondary
bacterial infection.75
Preventive measures for the treatment of ant
anaphylaxis include immunotherapy and re-sting
avoidance. Immunotherapy with imported fire ant
WBE is considered for adults and children with
systemic reactions to ants who have shown positive
results by skin testing or specific IgE antibodies.75
This recommendation is the same as the
immunotherapy recommended for hymenoptera
hypersensitivity. Children ≤16 years of age with
isolated cutaneous systemic reactions from ant
stings do not require immunotherapy because of the
low risk of subsequent systemic reactions.83, 84
Nevertheless, children with cutaneous reactions
from fire ant stings with a significant exposure risk
may be considered for treatment with imported fire
ant immunotherapy.75
The dosing schedule for imported fire ant
immunotherapy is not uniform because of the
rapidity of the build-up phase. Most expert
recommendation protocols indicate treatment once
or twice weekly until a maintenance dose is reached.
A maintenance dose of 0.5 ml of 1:100 (w/v)
imported fire ant WBE is recommended. If
treatment failure occurs, increased doses can be
considered.85 Some recommendations suggest 0.5 ml
of 1:10 (w/v) imported fire ant WBE as a
maintenance dose.86, 87 In endemic areas with a high
incidence of imported fire ant stings, the rapid
increase of the dose protocol or a rush schedule in
the maintenance phase is preferable to the
conventional schedule. A 2-day rush protocol with
imported fire ant immunotherapy showed good
safety and efficacy.86 A 1-day rush immunotherapy
protocol in children and adults was also safe and
effective.88, 89 Imported fire ant immunotherapy can
be advanced to the maintenance phase within only
1–2 days by rush protocol. The duration of
immunotherapy is usually 3–5 years. For patients at
risk of re-exposure, the recommendation for
discontinued immunotherapy is when the results of
skin testing or serum specific IgE for fire ants are
negative.90
Currently, there is insufficient data on the
efficacy of immunotherapy for ant species other
than the imported fire ant, and therefore, exposure
avoidance—such as not disturbing ant nests,
allowing nests to be removed by trained
professionals, avoiding walking barefoot or with
sandals, and wearing long pants and long-sleeved
shirts when working outdoors—should be
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Asian Pac J Allergy Immunol 2015;33:267-75
recommended to ant hypersensitivity patients.
11. Rhoades RB, Stafford CT, James FK, Jr. Survey of fatal
anaphylactic reactions to imported fire ant stings. Report of the
Acknowledgments
This review was a part of the study “Ant
hypersensitivity in Thailand: species and allergen
identification by detecting patients’ antibody
reaction to the tropical fire ant compared with the
imported fire ant” supported by the Thailand
Research Fund (TRF, grant number MRG5580064).
We thank Emeritus Prof. Dr. Wanpen Chaicumpa
for advice and for reviewing the manuscript. We
also thank Yudthana Samung for ant species
identification, and Vatcharin Nakphong for the fire
ant image (Figure 2). Thanks to Mr. Paul Adams for
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