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FLIES and MOSQUITOES (Order: Diptera)

Medical Toxicology of Natural Substances, by Donald G. Barceloux, MDCopyright © 2008 John Wiley & Sons, Inc.

IDENTIFYING CHARACTERISTICS

A single pair of wings characterizes the members of this order of blood - sucking insects (biting fl ies and mosqui-toes). A small knobbed structure that functions as a stabilizer appears behind the wings.

Common Name: Mosquito Scientifi c Name: Family Culicidae Physical Description: Mosquitoes have slender

bodies about 3 – 6 mm ( ∼ 0.1 – 0.2 in.) in length that is divided into a head, thorax, and abdomen. There are six long, thin legs with tiny claws at the ends and two wings covered with fl at scales. Most other fl ies have four wings. The head has two antennae and a long proboscis, which allows the mosquito to suck liquid from prey. The abdomen is a long, slender tube with eight pairs of spiracles.

Common Name: Sandfl y Scientifi c Name: Lutzomyia spp. ( Phlebotomus

spp.) Physical Description: Sand fl ies are tiny, hairy gnats

(1 – 3 mm/ ∼ 0.1 in.) that breed in dark, damp crev-ices during the day.

Common Name: Black Flies, Midges, Buffalo Flies Scientifi c Name: Simuliidae spp. Physical Description: Black fl ies, midges, and buffalo

fl ies are small (1 – 5 mm/ ∼ 0.1 – 0.2 in.) fl ies that have a hump - backed appearance.

Common Name: Stable Fly Scientifi c Name: Stomoxys calcitrans L. Physical Description: The stable fl y is physically

similar to the common housefl y.

Common Name: Horsefl y Family Scientifi c Name: Family: Tabanidae Physical Description: The horse fl y is a large

(20 mm/ ∼ 0.8 in.), slow - moving, blood - sucking insect that is usually easily repelled.

Common Name: Deer Fly Scientifi c Name: Chrysops spp. Physical Description: These stout - bodied, fast -

fl ying insects range in size from 6 – 30 mm ( ∼ 0.2 – 1.25 in.).

EXPOSURE

Geographic Distribution

Mosquitoes are aquatic breeders found worldwide, even beyond the Arctic Circle.

Important mosquito species (Diptera: Culicidae) include Aedes vexans Meigan, Aedes aegypti NPV, and Culex quinquefasciatus Say. The latter two mosquito species are distributed worldwide throughout the tropi-cal regions, whereas Aedes vexans Meigan inhabits North America, Asia, Africa, and Eurasia. The insect family Tabanidae comprises approximately 3,000 species of fl ies throughout the world except at the extreme

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northern and southern latitudes. Deer fl ies are found in wet, underdeveloped areas throughout the United States.

Behavior

Mosquitoes are most active during cooler, shady times of the day. These insects are attracted by smell as well as sight and temperature. 1 The female Aedes mosquito is responsible for most bites because the male Aedes mosquito lacks the penetrating mouth parts present on female mosquitoes. Attractants for female mosquitoes include moisture, carbon dioxide, warmth, odor, and estrogen. 2 Tabanids (horse fl ies, deer fl ies, clegs, gadfl ies) are wasp - or bee - like insects that often land unnoticed on humans while outdoors. Most females of the Tabani-dae family require a blood meal to complete egg devel-opment. Female sand fl ies feed exclusively on blood at night. Female deer fl ies feed on animals and occasion-ally on humans. These fl ies are attracted by carbon dioxide and large, dark, moving objects. Bites from deer fl ies ( Chrysops spp.) occur from late May until the middle of September. 3 These insects produce painful bites, and frequently bite unremittingly. The male taba-nids feed on nectar; they do not possess the modifi ed mouth parts capable of biting humans. Tabanids are holometabolous (i.e., undergo complete metamorpho-sis) insects that undergo four life stages (egg, larva or maggot, pupa, adult) similar to other true fl ies.

Black fl ies, midges, and buffalo fl ies breed in fast - fl owing streams. Black fl ies swarm in late spring and early summer. Biting midges swarm at sunset, forming dense clouds. This behavior distinguishes biting midges from the night - biting sand fl ies and day - biting black fl ies. The stable fl y is a blood - sucking fl y that breeds around farm animals and feeds at one spot for several minutes before moving to a different location.

PRINCIPAL TOXINS

Venom Composition

The salivary ducts of mosquitoes contain local anesthet-ics as well as antigens that can cause immediate or delayed hypersensitivity reactions in sensitized indi-viduals. 4 Salivary extracts of tabanids (horsefl ies, clegs, deerfl ies) include peptides and small proteins that inhibit thrombin activity in a dose - dependent manner. 5 The salivary secretions of Tabanus bovinus L. contain a 7 - kD peptide (tabanin) that is a thrombin inhibitor. Other anticoagulants present in the salivary secretions from deer fl ies ( Chrysops spp.) include platelet aggrega-tion inhibitors and glycoprotein IIb/IIIa fi brinogen receptor antagonists (chrysoptin). 6 The salivary secre-

tions of deer fl ies also contain a 69 kD IgE - binding protein capable of producing an anaphylactic reactions. 7

Venom Apparatus

Deer fl ies ( Chrysops spp.) and other tabanids (horse-fl ies, clegs) possess a scissor - like proboscis that incises the skin of the prey; they feed on the blood extruded from these wounds. Anticoagulants in the saliva help extract blood from the victim. Injected fl uids produce local tissue damage as well as mild local hypersensitivity reactions.

Dose Response

The reactions to bites from mosquitoes and fl ies result from hypersensitivity reactions; therefore, the response to these bites is not dose - related.

HISTOPATHOLOGY AND PATHOPHYSIOLOGY

Clinical and experimental data suggests that various reactions to mosquito bites result from sensitization to the mosquito saliva injected into the skin during feeding. 8 – 10 These reactions include both IgE - mediated and T - lymphocyte - mediated hypersensitivity responses. The size of the immediate wheal and fl are reaction cor-relates to the presence of IgE - specifi c antibodies, and there are strong cross - reactive skin and IgE - mediated responses among common mosquito species. 11 The immediate skin reaction involves an irregular, central punctate lesion in the epidermis surrounded by super-fi cial edema. 12 Marked vasodilation develops in the dermis along with perivascular infi ltration of leukocytes (polymorphonuclear, eosinophils). In addition to an Arthus - type mechanism, cutaneous late - phase reactiv-ity and cell - mediated immunity may also be involved in the formation of delayed papules. 13 Frequent exposure to mosquito bites may produce blocking (IgG) anti-bodies and desensitization to the bites. 14 The saliva of deer fl ies contains immunogenic proteins that cause IgE - mediated anaphylactic reactions. 7

CLINICAL RESPONSE

Cutaneous responses to mosquito bites range from immediate wheals and delayed papules to severe Arthus - type reactions with systemic complaints. 15 Individual responses to mosquito bites are highly variable; the type of response includes vesicular, urticarial, eczematoid, and granulomatous lesions. These lesions may become bullous and excoriated. The initial mosquito bite causes

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no response, but subsequent bites produce delayed papular lesions. The typical response to mosquito bites in sensitized individuals involves the formation of pru-ritic wheals 2 – 10 mm ( ∼ 0.1 – 0.4 in.) in diameter. Pruritic papules commonly develop several hours after the wheal and fl are reaction, and the symptoms peak over 24 – 48 hours. These delayed papules typically resolve over several days, but occasionally these papules may persist a few weeks. Repeat mosquito bites can produce cutaneous reactions at old bite sites. Large local reac-tions occur occasionally. The appearance and intensity of delayed hypersensitivity reactions decreases with age and the frequency of bites. 16

Rarely in sensitized asthmatic patients, mosquito bites may produce Arthus - type reactions (joint swelling, fever, adenopathy, nausea, headache) or anaphylaxis (wheezing dizziness, lethargy, urticaria, angioedema, hypotension). 17,18 A seasonal bullous eruption of the lower legs has been associated with bites by the Aedes detritus Haliday mosquito. 19 Mosquito bites can trans-mit fi lariasis, dengue fever, malaria, yellow fever, chi-kungunya fever, and viral encephalitis to humans. 20,21 However, mosquitos probably do not transmit HIV disease because of the absence of T 4 antigen on cell surfaces and low titer of the virus in human body fl uids. 22

Rarely, severe anaphylactic responses (e.g., hypoten-sion, dyspnea) may occur after bites from horse fl ies ( Tabanus spp.) 23,24 or from deer fl ies ( Chrysops spp.). 25 Common house fl ies ( Musca domestica L.) are rarely associated with respiratory sensitization in asthmatic patients. 26 Black fl ies, midges, and buffalo fl ies produce an extremely painful, pruritic, erythematous lesion that usually begins one hour after the bite. Later, the lesion may develop into a nodular, eczema - like patch or a hard pigmented nodule.

DIAGNOSTIC TESTING

Clinical abnormalities are not usually associated with bites from these insects other than those associated with infectious or allergic processes. There are no commer-cial biomarkers for these insect bites.

TREATMENT

Supportive care for mosquito and fl y bites is similar to the treatment of fl ea bites. Washing horse and stable fl y bites with an antiseptic solution [e.g., povidone - iodine (Betadine ® , Purdue Pharma, Stamford, CT)] or soap and water and the application of a topical antibiotic ointment may prevent infection. Topical corticosteroid ointment may reduce swelling, redness, and itching asso-ciated with the bites, but the use of topical antihistamine

creams is probably not effi cacious. 9 Oral antihistamines (e.g., cetirizine 10 mg) reduce the pruritus and wheal associated with mosquito bites, but these antihistamines do not alter the intensity or duration of the delayed symptoms. 27 A volunteer study suggests that dilute ammonia solution (3.6%) applied minutes after the mosquito bite may reduce the wheal and fl are reac-tion. 28 Other topical agents include preparations with menthol and camphor.

Insect repellents containing DEET ( N,N - diethyl - m - toluamide) effectively repel biting insects, such as mos-quitos, biting fl ies, gnats, chiggers, and ticks. Currently available non - DEET repellents do not provide the duration of protection from mosquito or fl y bites com-pared with DEET - based repellents. 29 The repellent should be applied to all exposed areas of the skin except the eyelids and any skin lesions. Field entomological studies indicate that electronic mosquito repellants have no effect on preventing mosquito bites. 30

References

1. Metry DW , Hebert AA . Insect and arachnid stings, bites, infestations, and repellents . Pediatr Ann 2000 ; 29 : 39 – 48 .

2. Brown AW . The attraction of mosquitoes to hosts . JAMA 1966 ; 196 : 249 – 252 .

3. Pratt GK , Pratt HD . Notes on deer fl ies and horse fl ies (Diptera: Tabanidae) from southern Vermont . J Am Mosq Control Assoc 1986 ; 2 : 365 – 367 .

4. Newsome WH , Jones JK , French FE , West AS . The isola-tion and properties of the skin - reactive substance in Aedes aegypti oral secretion . Can J Biochem 1969 ; 47 : 1129 – 1136 .

5. Kazimirova M , Sulanova M , Kozanek M , Takac Pk, Labuda M , Nuttall PA . Identifi cation of anticoagulant activities in salivary gland extracts of four horsefl y species (Diptera, Tabanidae) . Haemostasis 2001 ; 31 : 294 – 305 .

6. Reddy VB , Kounga K , Mariano F , Lerner EA . Chrysoptin is a potent glycoprotein IIb/IIIa fi brinogen receptor antag-onist present in salivary gland extracts of the deerfl y . J Biol Chem 2000 ; 275 : 15861 – 15867 .

7. Hemmer W , Focke M , Vieluf D , Berg - Drewniok B , Gotz M , Jarisch R . Anaphylaxis induced by horsefl y bites: iden-tifi cation of a 69 kd IgE - binding salivary gland protein from Chrysops spp. (Diptera, Tabanidae) by Western blot analysis . J Allergy Clin Immunol 1998 ; 101 : 134 – 136 .

8. Hudson A , Bowman L , Orr CM . Effects of absence of saliva on blood feeding by mosquitoes . Science 1960 ; 131 : 1730 – 1731 .

9. Reunala T , Brummer - Korvenkontio H , Lappalainen P , Rasanen L , Palosuo T . Immunology and treatment of mos-quito bites . Clin Exp Allergy 1990 ; 20 (suppl 4 ): 19 – 24 .

10. McKiel JA . Sensitization to mosquito bites . Can J Zool 1959 ; 37 : 341 – 351 .

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11. Peng Z , Simons FE . Cross - reactivity of skin and serum specifi c IgE responses and allergen analysis for three mos-quito species with worldwide distribution . J Allergy Clin Immunol 1997 ; 100 : 192 – 198 .

12. Goldman L , Rockwell E , Richfi eld DF . III . Histopatho-logical studies on cutaneous reactions to the bites of various arthropods . J Invest Dermatol 1952 ; 19 : 514 – 525 .

13. Tokura Y , Tamura Y , Takigawa M , Koide M , Satoh T , Saka-moto T , Horiguchi D , Yamada M . Severe hypersensitivity to mosquito bites associated with natural killer cell lym-phocytosis . Arch Dermatol 1990 ; 126 : 362 – 368 .

14. Ailus K , Palosuo T , Brummer - Korvenkontio M , Rantanen T , Reunala T . Demonstration of antibodies to mosquito antigens in man by immunodiffusion and ELISA . Int Arch Allergy Appl Immunol 1985 ; 78 : 375 – 379 .

15. Rockwell EM , Johnson P . The insect bite reaction. II. Eval-uation of the allergic reactions . J Invest Dermatol 1952 ; 19 : 137 – 155 .

16. Oka K , Ohtaki N . Clinical observations of mosquito bite reactions in man: a survey of the relationship between age and bite reaction . J Dermatol 1989 ; 16 : 212 – 219 .

17. Gaig P , Garcia - Ortega P , Enrique E , Benet A , Bartolome B , Palacios R . Serum sickness - like syndrome due to mosquito bites . Invest Allergol Clin Immunol 1999 ; 9 : 190 – 192 .

18. Gluck JC , Pacin MP . Asthma from mosquito bites: a case report . Ann Allergy 1986 ; 56 : 492 – 493 .

19. Walker GB , Harrison PV . Seasonal bullous eruption due to mosquitoes . Clin Exp Dermatol 1985 ; 10 : 127 – 132 .

20. Thwing J , Skarbinski J , Newman RD , Barber AM , Mali S , Roberts JM , et al. Malaria surveillance — United States, 2005 . MMWR Surveill Summ 2007 ; 56 : 23 – 40 .

21. Centers for Disease Control and Prevention (CDC) . West Nile virus update — United States, January 1 – July 24, 2007 . MMWR Morb Mortal Wkly Rep 2007 ; 56 : 740 – 741 .

22. Iqbal MM . Can we get AIDS from mosquito bites? J La State Med Soc 1999 ; 151 : 429 – 433 .

23. Freye HB , Litwin C . Coexistent anaphylaxis to Diptera and Hymenoptera . Ann Allergy Asthma Immunol 1996 ; 76 : 270 – 272 .

24. Solley GO . Allergy to stinging and biting insects in Queensland . Med J Aust 1990 ; 153 : 650 – 654 .

25. Hrabak TM , Dice JP . Use of immunotherapy in the man-agement of presumed anaphylaxis to the deer fl y . Ann Allergy Asthma Immunol 2003 ; 90 : 351 – 354 .

26. Focke M , Hemmer W , Wohrl S , Gotz M , Jarisch R , Kofl er H . Specifi c sensitization to the common housefl y ( Musca domestica ) not related to insect panallergy . Allergy 2003 ; 58 : 448 – 451 .

27. Karppinen A , Kautiainen H , Petman L , Burri P , Reunala T . Comparison of cetirizine, ebastine and loratadine in the treatment of immediate mosquito - bite allergy . Allergy 2002 ; 57 : 534 – 537 .

28. Zhai H , Packman EW , Maibach HI . Effectiveness of ammonium solution in relieving type I mosquito bite symptoms: a double - blind, placebo - controlled study . Acta Derm Venereol 1998 ; 78 : 297 – 298 .

29. Fradin MS , Day JF . Comparative effi cacy of insect repel-lents against mosquito bites . N Engl J Med 2002 ; 347 : 13 – 18 .

30. Enayati AA , Hemingway J , Garner P . Electronic mosquito repellents for preventing mosquito bites and malaria infection . Cochrane Database Syst Rev 2007 ;( 2 ): CD005434 .