Fire ant hypersensitivity

Fire Ant Venom Hypersensitivity
Natthiya Pholmoo, M.D.
Allergy and Immunology Unit
King Chulalongkorn Memorial Hospital

Backgrounds
• Ants are well-recognized insects belong to the family Formicidae within the order
Hymenoptera the same with bees and wasps.
• There currently 12,500 ant species in 290 genera belonging to 21 subfamilies have
been recorded.
• In Thailand, there are as many as 247 species distributed among 55 genera in 9
subfamilies of ants have been recorded.
• A new species of the ant genus Myrmecina Curtis, Myrmecina raviwongsei
Jaitrong, Samung, Waengsothorn et Okido ; มดอาจารย์รวิน has been recorded in
2019.
• The most common “fire ant species found in Thailand is S. geminata
(tropical fire ant, TFA)
Potiwat R, Sitcharungsi R. Ant allergens and hypersensitivity reactions in response to ant stings. Asian Pac J Allergy Immunol. 2015;33(4):267-275.
Jaitrong W, Nabhitabhata J. A List of Known Ant Species of Thailand (Formicidae:Hymenoptera). Thailand Natural History Museum J. 2005;1(1):9-54
Jaitrong W., Samung Y., Waengsothorn S., Okido H. A new species of the ant genus Myrmecina Curtis, 1829 (Hymenoptera: Formicidae, Myrmicinae)
from Thailand . Number: 383, Pages: 1 - 7

Srisong H, Daduang S, Lopata AL. Current advances in ant venom proteins causing hypersensitivity
reactions in the Asia-Pacific region. Mol Immunol. 2016;69:24-32. doi:10.1016/j.molimm.2015.11.003

• Solenopsis species, Formica, Myrmecia, Tetramorium,
Pogonomyrmex, Pachycondyla, Odontomachus, Rhytdoponera,
Pseudomyrmex, and Hypoponera are ant genera that have been
reported to cause serious hypersensitivity reaction.
• Solenopsis, especially S. invicta and S. richteri called imported fire
ants are genera of ants well-known for causing life-threatening
allergic reaction.
ผศ. พญ. รวีรัตน์ สิชฌรังษี และคณะ. 2557. การศึกษาการแพ้มดในประเทศไทยโดยการสืบหาสายพันธุ์และสารก่อภูมิแพ้ของมด
ด้วยการตรวจหาปฏิกิริยาของภูมิคุ้มกันผู้ป่วยต่อสารสกัดจากมดคันไฟเปรียบเทียบกับสารสกัดจากมดคันไฟจากต่างประเทศ

Thailand
• The most common fire ant species found in Thailand is
Solenopsis geminata (tropical fire ant)
• The most common ants causing anaphylaxis
- Solinopsis geminate มดคันไฟ
- Tetraponera Rufonigra มดตะนอยอกส้ม
- Odontoponera denticulata มดตาชื่นดา

Species of ants most offen responsible for
anaphylaxis in Thai patient

• S. geminata have a
polymorphic size of
3–8 mm body length.
• The body has a
reddish brown color
and is mostly smooth
and shiny.
• The head of the
S. geminate is divided
into two notches.

Nest structure
• Solenopsis geminata nests were flat
compared to S. Invicta
• Often found in an opened area, dry soil, rather than in the shadow
area under the trees.
• S.geminata were likely to be opened to the sun, warm and not too
humid. Plant crops that they were associated were rice, corns,
peanuts, rambutan, mangosteens, vegetables (e.g. morning glories,
tomato, limes), and marigold flowers
Mingkwan Nipitwattanaphon. 2017. Colony’s queen number of the invasive tropical fire ant,
Solenopsis geminate in Thailand and some ecological factors associated with social form

Nest structure
• Their nests have many holes on the top.
• The colony usually occupy >1m in diameter and could be >50 cm
depth depending on the nature of the soil.
• They often make the nest in a very safe place from flooding, or
disturbing by human, e.g. under the concrete of the building, or
under the roots of the trees or dead trees

Characteristics of fire ants nests. Nests are flat and have many entrances scatter around
(A-B). Nests can be deeper than 30cm (C-D). Red arrows indicate larval chambers.

Fire ant nest are often found in a very secure place, e.g. under the hard soil (A), in the
palm root (B) or dead tree’s root (C), and in the concrete of the building (D).

Imported fire ant
• Imported fire ants were introduced from South America and spread to
Southeastern USA since 1920.
• Currently, they have become endemic in some areas of Asian
countries such as China, HongKong, and some part of Australia.
• S. invicta is known as red imported fire ant.
• The risk of imported fire ant stings in people living in endemic area is as
high as 30-60% with 0.16-16% risk of severe reactions.
• the imported fire ant attacks with little warning. Firmly grasping the skin
with its powerful mandibles, the fire ant arches its back, inserts its stinger
into the flesh, and injects venom from the attached venom sac.
• There is no report of imported fire ant in Thailand.

Ant allergens
• The venom of imported fire ant is unique because it has low protein
content and high concentration of piperidine toxin that consists of
90-95% water-soluble alkaloids, 2-methyl-6-alkylpiperidines.
• Majority of the fire ant venom consists of 90–95% basic piperidine
alkaloids that are highly cytotoxic, neurotoxic and hemotoxic.
• The alkaloid part of the S. invicta venom causes a sterile pustule at the
sting site.
• Each S. invicta sting transfers 0.04 to 0.11 µL of venom and 10 to 100 ng
of proteins that can cause specific IgE antibody production..

Sterile pustule
• Pathognomonic sign for
S. invicta
• Frequently the pustules are
clustered (multiple stings)
Villada G, Hafeez F, Ollague J, Nousari CH, Elgart GW. Imported fire ant envenomation: A
clinicopathologic study of a recognizable form of arthropod assault reaction. J Cutan Pathol.
2017;44(12):1012-1017. doi:10.1111/cup.13036

S. invicta allergens
The protein part is composed of 4 major allergens
• Sol i 1 is a 37-kDa protein with phospholipase A1 activity that
comprises 2–5% of the total venom protein.
• 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 of
wasp venom proteins 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.
Potiwat R, Sitcharungsi R. Ant allergens and hypersensitivity reactions in response to ant stings. Asian Pac
J Allergy Immunol. 2015;33(4):267-275.
Stafford CT. Hypersensitivity to fire ant venom. Ann Allergy Asthma Immunol. 1996;77(2):87-99.
doi:10.1016/S1081-1206(10)63493-X

S. invicta allergens
• Most patients react to all four allergens.
• While most fire ant whole body extracts appear to contain relevant
Sol i allergens, the concentrations are reduced by the relatively large
amount of extraneous body proteins.
Stafford CT. Hypersensitivity to fire ant venom. Ann Allergy Asthma Immunol.
1996;77(2):87-99. doi:10.1016/S1081-1206(10)63493-X

Sol i 1 allergen
• is a 37-kDa protein with phospholipase A1
activity that comprises 2–5% of the total
venom protein.
• is also found in vespid venoms and belongs to
the lipoprotein lipase family
• There is some evidence of the IgE reactivity
against protein determinants and showed some
cross-reactivity with yellow jacket, wasp and
honeybee venom phospholipase.

Sol i 2 allergen
• This allergen comprises 67% of the total venom proteins.
• It is composed of two identical monomers, which have 3
intra- and 1 inter-molecular disulfide bonds and contains
carbohydrate determinants, dissimilar to the other sol allergens.
• other similar venom proteins to Sol i 2 of the Solenopsis species are
S.geminata (Sol g 2), S.richteri (Sol r 2) and S. saevissima (Sol s 2)
• Sol i 2 generate the production of IgE antibody in about one-third of
individuals stung by fire ants.

Sol i 3 allergen
• is a 24-kDa protein that comprises 20%
of the total venom protein.
• Sol i 3 demonstrates its relationship to members of the antigen 5
protein family of vespid venom proteins
but does not show crossreactivity with vespid venom antigen 5

S. geminata allergens
S. geminata venom had 4 allergenic proteins
• Sol gem 1
• Sol gem 2
• Sol gem 3
• Sol gem 4
After evaluating Sol gem 2 under non-reducing and reducing
conditions, its native form was indicated to be dimer with molecular
weight of 28 and 15 kDa with allergenic properties similar to Sol i 2
of S. invicta.
Sukprasert, Sophida & Uawonggul, Nunthawun & Jamjanya, Tasanee & Thammasirirak, Sompong & Daduang, Jureerut & Daduang, Sakda.
(2012). Characterization of the allergen Sol gem 2 from the fire ant venom, Solenopsis geminata. Journal of Venomous Animals and Toxins
including Tropical Diseases. 18. 10.1590/S1678-91992012000300010.

Coomasie Brilliant Blue G-250 stained 13% SDS-PAGE showed the protein composition of S. invicta
(imported fire ant-IFA) and S. geminata (tropical fire ant-TFA) extracts (20 g per lane) with relative
molecular masses (Mr) ranged from 10 to 260 (relative to the molecular weight marker, M).
• Tropical fire ant extract revealed
more than 20 bands of protein
ranged from 10 to 200 kDa
• Imported fire ant allergens appeared
to have only 2 major bands between
25 to 35 kDa.
ผศ. พญ. รวีรัตน์ สิชฌรังษี และคณะ. 2557. การศึกษาการแพ้มดในประเทศไทยโดยการสืบหาสายพันธุ์และสารก่อภูมิแพ้ของมดด้วยการตรวจหาปฏิกิริยาของภูมิคุ้มกันผู้ป่วยต่อสารสกัดจากมดคันไฟเปรียบเทียบกับสารสกัดจากมดคันไฟจากต่างประเทศ
Potiwat R, Tanyaratsrisakul S, Maneewatchararangsri S, et al. Solenopsis geminata (tropical fire ant) anaphylaxis among Thai patients: its allergens and specific IgE-reactivity. Asian Pac J
Allergy Immunol. 2018;36(2):101-108. doi:10.12932/AP-100217-0012

Numbers on the left column indicate molecular weight of the
protein. Numbers on the top row indicate patient individual
ordered. Filled circle ( ) represents protein band reacted with
serum IgE from each patient shown in Western blot analysis.
• The common IgE-specifc reactive
bands of S. geminata (presented in
>80% of ant allergic patients’ serum)
had estimated molecular masses of
26, 55 and 75 kDa which suggested
that these three proteins might be
the major allergens of TFAs.

• The 26 and 55 kDa allergens
may induce the production
of cross-reactive IgE that
can recognize allergens from
both S. geminata and
S.Invicta.
l
e
r
g
e
n
s
f
r
o
m
b
o
t
h
S
.
g
e
m
i
l
e
r
g
e
n
s
f
r
o
m
b
o
t
h
S
.
g
e
m
i
Potiwat R, Tanyaratsrisakul S, Maneewatchararangsri S, et al. Solenopsis
geminata (tropical fire ant) anaphylaxis among Thai patients: its allergens and
specific IgE-reactivity. Asian Pac J Allergy Immunol. 2018;36(2):101-108.
doi:10.12932/AP-100217-0012

Cross-reactivity among Solenopsis species
• 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.
• Sol i 2 has 72.3% amino acid sequence homology with Sol gem 2 and
78.2% sequence homology with Sol r 2

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 cross reactivity among major proteins of vespids
(yellow jackets) and S. invicta.

Fire Ant hypersensitivity
• The alkaloids do not generate IgE antibody responses but the
allergenic proteins in the venom, which comprise only 0.01% of the
venom by weight can induce IgE production in allergic patients to fire
ant stings
• the confirmation of ant anaphylaxis in suspected patients is currently
based on a skin test or specific IgE against S. invicta whole body
extract (WBE), the only available commercial tests for ant allergy
doi:10.1016/S1081-1206(10)63493-X

• A possible explanation for variability among imported fire ant whole body
extract preparations may be seasonal variation in antigenic activity.
• A more than 100-fold difference in phospholipase activity has been
reported in extracts pre-pared from ants collected in early
summer compared with winter.
doi:10.1016/S1081-1206(10)63493-X

Ant sting and venom isolation
• The ant venom is usually injected from a poison gland located at the
posterior part of the ant (gaster)
• Ant whole body extract (WBE) or the induced secretion of poison
from the posterior gland has been used for ant immunotherapy.
Sukprasert, Sophida & Uawonggul, Nunthawun & Jamjanya, Tasanee & Thammasirirak, Sompong & Daduang, Jureerut & Daduang, Sakda. (2012).
Characterization of the allergen Sol gem 2 from the fire ant venom, Solenopsis geminata. Journal of Venomous Animals and Toxins including Tropical Diseases. 18. 10.1590/S1678-
91992012000300010.

Clinical presentation
Immediate reactions : occur within 1–4 hours after ant stings
• normal local reactions : pain, swelling, erythema, heat, and sterile
pustules at sting sites [S. invicta] result of toxic alkaloids in the venom.
• large local reactions [17-56%] : a reaction larger than 10 cm in
diameter persisting for longer than 24 hours
• generalized cutaneous reactions : pruritus and urticarial
• systemic reactions : anaphylaxis are mediated by specific IgE
antibodies to venom allergens
Stafford CT. Hypersensitivity to fire ant venom. Ann Allergy Asthma Immunol. 1996;77(2):87-99. doi:10.1016/S1081-1206(10)63493-X

Clinical presentation
Delayed reactions : usually occur more than 4 hours after ant stings
• Dermatitis
• Arthralgia
• Lymphadenopathy
• Renal abnormalities
• Vasculitis
• Serum sickness which consists of angioedema, urticaria, malaise and
fever about 7 days after the sting

Diagnosis of ant-induced hypersensitivity
• Identification of the causative ant should be determined by an
entomological specialist.
• 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
• The confirmation of ant anaphylaxis in suspected patients is currently
based on a skin test or specific IgE against S. invicta whole body
extract (WBE)

In vivo test
• Skin-prick test is performed using a concentration of 1:1000 (w/v) of
imported fire ant WBE testing.
• 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.
• 29 % of adults with a history of fire ant exposure without systemic
reactions had a positive skin-test result.

In vitro test
• 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.
• 24% of non-allergic control cases had positive specific-IgE test results
for imported fire ant venom

• The ant-sting challenge test is used for patients with a history of ant
anaphylaxis but negative skin testing and serum specific IgE results.

Management of ant-induced hypersensitivity
Immediate treatment for anaphylaxis
• Epinephrine at a dosage of 0.01 mg/kg to a maximum of 0.3 mg for
children and 0.5 mg for adults.
• Antihistamines
• Bronchodilators
• Late-phase anaphylaxis can be prevented by corticosteroids.
• Supportive treatments should follow standard guidelines for
anaphylaxis, including fluid resuscitation, oxygen therapy.

Management of ant-induced hypersensitivity
• Local reactions
• wound dressing
• topical or systemic antibiotics for secondary infection
• cold compression to reduce local swelling
• 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.
• Large local reactions
• elevation of the affected extremity
• Antihistamines
• corticosteroids in severe cases
• Antibiotics usually are not necessary.
• no specific treatment is usually necessary.
Stafford CT. Hypersensitivity to fire ant venom. Ann Allergy Asthma Immunol. 1996;77(2):87-99. doi:10.1016/S1081-1206(10)63493-X

Exposure avoidance
• Do not disturbing ant nests.
• Avoid going barefoot or wearing sandals.
• Wear gloves and protective footwear while gardening.
• Wearing long pants and long-sleeved shirts when working
• Allowing nests to be removed by trained professionals
• Pest control and elimination of ant nests from home areas

Immunotherapy
• 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.

Immunotherapy
• 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.
• Some recommendations suggest 0.5 ml of 1:10 (w/v) imported fire ant
WBE as a maintenance dose
• 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.
Potiwat R, Sitcharungsi R. Ant allergens and hypersensitivity reactions in response to ant stings. Asian Pac J
Allergy Immunol. 2015;33(4):267-275.
Srisong H, Daduang S, Lopata AL. Current advances in ant venom proteins causing hypersensitivity reactions
in the Asia-Pacific region. Mol Immunol. 2016;69:24-32. doi:10.1016/j.molimm.2015.11.003

Immunotherapy
• Immunotherapy seems to be very effective for at least 4 years
• only 3% of re-sting patients developed anaphylactic reactions, and
might be increased after discontinuing therapy, but reported to
increase to not more than 10%

Fire ant hypersensitivity

Recomendados

Recomendados

Mais conteúdo relacionado

Mais procurados

Mais procurados (20)

Semelhante a Fire ant hypersensitivity

Semelhante a Fire ant hypersensitivity (20)

Mais de Chulalongkorn Allergy and Clinical Immunology Research Group

Mais de Chulalongkorn Allergy and Clinical Immunology Research Group (20)

Último

Último (20)

Fire ant hypersensitivity