Arthropod Envenomation

Michael R. Loomis, DVM, MA, DACZM North Carolina Zoological Park Hymenoptera Envenomation Order Hymenoptera

Family Vespidae- wasps Family Formicidae- ants

Familt Mutillidae- velvet ants Family Apidae- bees • Stinger is a modified ovipositor Bee and Wasp Venom Components

• Proteins, peptides and • Apitoxin – 52% Melitten (potent anti- amines inflammatory agent that – Phospholipase increases production of cortisol) – Histamine – 10-12% Phospholipase A2 – Bradykinin – 2-5% Aldolapin (blocks – cyclooxygenase) Acetylcholine – 1-3% Hyuronidase – Dopamine – 0.5-2% Histamine – Seratonin – 1-2% Dopamine and noradrenaline – Mast cell degranulating – 2% Protease-inhibitors peptide – Apamine increases cortisol – Mastoparan production, mild neurotoxin Ant Venom Components

• Fire ants- 95% alkaloid (Unique among ants) • Most other ants, similar to bee and wasp venom • Harvester ant venom contains a hemolysin Venom Toxicity

Family Common Name LD 50 (mg/kg) Apidae Honey bee 2.8 Mutillidae Velvet ant 71.0 Vespidae Paper wasp 2.4 Vespidae Yellowjacket 3.5 Formicidae Harvester ant 0.66 Formicidae Maricopa Harvester ant 0.12 Morbidity and Mortality Bees and Wasps • In US, 9.3 million ant • 17-56% produce local stings and 1 million reactions stings of other • Hymenoptera/year 1-2% produce generalized reactions • More deaths/year than any other type of • 5% seek medical care envenomation • 30-120 deaths from • Most deaths are the wasp and bee result of Anaphylaxis stings/year Local Reactions

• Pain • Edema which may extend 10 cm from sting • +/- bleeding • Pruritis • Sensation of warmth due to vasodilation • Nausea/vomiting Generalized Reactions- Anaphylaxis

• Urticaria • Target organs (IgE-mediated • Confluent red rash allergic reaction) • Shortness of breath or – Skin- urticaris wheezing – Respiratory System • Bronchospasm • Weakness, syncope • Laryngospasm • Anxiety, confusion – Vascular system • Chest pain • Vasodilation • Angioedema • Twice as many anaphylactic reactions from wasps than bees • Possible DIC

Generalized Reactions- Toxic

• Can result from 30 • Melittin, phospholipase vespid stings or 200 A2 and hyluronidase honey bee stings responsible for most • Massive envenomations toxic signs in adults results in > – Vomiting 15% mortality – Diarrhea • 20 honey bee stings/kg – Shock lethal for humans – Hemoglobinuria – Rhabdomyolysis – Multiorgan failure Generalized Reactions- Toxic

• Acute renal failure • Kounis syndrome – Acute tubular necrosis (allergic myocardial – Direct nephrotoxic ischemia and infarction) effects – Inferior ST-segment – Interstitial nephritis from elevation hypersensitivity reaction – Pigment nephropathy (Rhabdoymolysis or intravascular hemolysis) Fire ants

• 1989- 32 deaths from fire ants • “Pathnpneumonic” sterile pustules • Little protein so anaphylaxis uncommon • Can survive as many as 5000 stings

Harvester Ants

Maricopa harvester ant has the most toxic insect venom

Single sting of harvester ant Treatment- Generalized- Anaphylaxis

• Antihistamines – Diphenhydramine – Cimetadine (IV) if unresponsive to Diphenhydramine • Bronchodilators – Epinephrine – Albuterol – Theophylline • Corticosteroids Treatment- Local

• Remove stinger • Diphrenhydramine • Ice or cool pack • Elevate extriminity Centiped Envenomation Class Chilopoda

• 3000 species • Single pair of legs/body segment • Predominately nocturnal • Warm temperate and tropical regions • Scolopendra most dangerous genus • Venom delivered by forcipuels, modified pair of legs behind the mandibles • Venom components: – 5-hydroxytryptamine – hemolytic phospholipase A – a cardiotoxic protein – a cytolysin • Unknown frequency of stings

Morbidity and Mortality

• Systemic reactions – ECG changes suggestive of Ischimia – Rhabdomyalysis – Proteinuria • Fatalities extremely rare – 7 year old Phillipino girl stung by S. subspinipes – 5 fatalities reported in U.S from 1991-2001

Symptoms and Signs of Envenomation

• Severe pain • Local tissue swelling • Redness • Swollen, painful lymph nodes • Headache • Palpitations • Nausea and/or vomiting • Anxiety • Local puritis Treatment

• Systemic analgesics as needed • Local injectable anesthetics (e.g. lidocaine) • Update tetanus vaccination • Monitor for local infection • Symptomatic treatment for systemic signs Milliped Envenomation Class Diplopoda

• 7000 species • 2 pairs of legs/body segment • Do not have biting mouthparts or fangs Morbidity and Mortality

• No documented deaths • Secrete defensive irritating liquid from pores along sides • Secretions contain – Benzoquinones – Aldehydes – Hydrocyanic acid – Phenols – Terpenoids – Nitroethylbenzenes Signs and Symptoms

• Local erythema • Mild edema • Vessicles • Rarely, cracked skin that may slough and heal • Conjunctivitis

Treatment

Scorpion Envenomation • 1500 species • 50 species dangerous to humans • Flattened, elongated body • 1 pair of claws • 4 pairs of legs • Segmented tail with poisonous spike at end • Most dangerous species belong to family Buthidae Scorpions Known to be Lethal to Humans

Genus Geographical Location • Buthus Mediterranean area • Parabuthus Western and Southern Africa • Mesobuthus Throughout Asia • Buthotus Southern Africa and SE Asia • Tityus Central and South America • Leiurus North Africa and Middle East • Androctonus North Africa to SE Asia • Centruroides SW U.S., Mexico, Central America, Caribbean Frequency of Stings

• Occur in temperate and tropical regions (50°N to 50°S latitude) • In 2006 16,231 reported stings in U.S. • Only 1 of 30 species of scorpions in U.S. dangerous to humans (Centruroides) Lethal Stings

• Most fatalities within 24 hours of sting from respiratory and/or cardiovascular failure – < 1% Centuroides stings in adults are fatal – 25% children under 5 die if not treated • Mexico 1000 deaths /year • U.S. 4 deaths in 11 years Venom

• Contains multiple toxins and other compounds – Neurotoxins -Glycosaminoglycans – Cardiotoxins -Histamine – Nephrotoxins s -Serotonin – Hemolytic toxins -Tryptophan – Phosphodiesterases -Cytokine releasers – Phospholipases – Hyaluronidases Neurotoxins

• Most Potent toxin components • Cause impairment in nerves, muscles and heart by altering ion channel permeability • 2 classes – Long-chain polypeptide • Stabilizes sodium channels in open position causing prolonged firing of somatic, sympathetic and parasympathetic neurons • Release of excessive neurotransmitters – Short polyprptide • Blocks potassium channels Venom Toxicity

SPECIES LD50 (mice) mg/kg Leiurus quinquestriatus (Middle East) 0.25 Androctonus crassicauda (Saudi Arabia) 0.08-0.5 Centruroides noxius (Mexico 0.26 Tityus serrulatus (Brazil) 0.43 Centruroides sculpturatus (SW U.S.) 1.12 Mesobuthus eupeus (Iran) 1.45

Mouse LD50 of < 1.5mg/kg considered potentially lethal for humans Signs and Symptoms

• Most common are: – Mydriasis – Nystagmus – Hypersalivation – Dysphagia – Restlessness Signs and Symptoms

• Sympathetic Override • Parasympathetic – Tachycardia Symptoms – Hypertension – Hypotension – Hyperthermia – Bradycardia – Pulmonary Edema – Salivation – Lacrimation – Urination – Defecation – Gastric Emptying Signs and Symptoms

• Cranial Nerve Effects • Somatic effects – Roving or rotary eye – Restlessness movements – Muscle jerking – Blurred vision – True seizures – Tongue fasciculations (Centruroides) – Loss of pharyngeal muscle control Treatment

• Local RX – Negative-pressure extractor – Ice bags (first 2 hours) – Local wound care – Immobilize affected body part below level of heart – Calm the patient – Lymphatic-venous compression wrap if medical RX is delayed – Topical or local anesthetic – Muscle relaxers for severe spasms – =/- tetanus prophylaxis, antibiotics Treatment

• Systemic Treatment – ABC’s – O2 – IV fluids – Cardiac drugs as necessary – Atropine (counters venom-induced parasympathetic effects) Treatment

• Antivenom – Treatment of choice Spider Envenomation Over 3000 Species of Spiders

• 98-99% of spider bites are harmless • 4 Genera have produced lethal bites • 3 additional genera are probably capable of producing lethal bites • Symptoms can include: – Necrotic wounds – Systemic toxicity – Death Lethal Genera

• Atrax- Australian funnel-web spiders • Latrodectes- Widow spiders • Loxosceles- Recluse spiders • Phoneutria- Wandering spiders Potentially Lethal Genera

• Hadronyche- Australian funnel-web spiders • Missulena- Mouse spiders • Sicaritus- Six-eyed sand spider Types of Venom

• Neurotoxic – Widow spiders- Latrotoxins – Australian funnel web and mouse spiders- open sodium channels – Brazilian wondering spiders- attacks multiple types of ion channels, serotonin • Necrotic venom – Family Sciariidae –recluse and six-eyed sand spiders. Produce dermonecrotic compound sphingomyelinase

Venom Delivery

• Two chelicerae, each with two segments, the fang and the basal portion. – Fang penetrates the skin – Basal portion includes all or part of the spider's venom glands, which can be squeezed under voluntary control by the spider to force venom out of the glands and into the wound Widow spiders

• Genus Latrodectus

Black widow spider Large geographical range

Widow spiders

• Genus Latrodectus – Latrotoxins-cause release of acetylcholine • Stimulates muscle contractions • painful abdominal cramps • interfering with respiration Katipo spider • 5% death rate prior to development of antivenom • 63 deaths in US from 1950- 1989

Widow spiders

• Local pain may be followed by localized or generalized severe muscle cramps, abdominal pain, weakness, and tremor • Large muscle groups (such as shoulder or back) are often affected, resulting in considerable pain. • In severe cases, nausea, vomiting, fainting, dizziness, chest pain, and European black widow spider respiratory difficulties may follow.

Widow spiders

• In some cases, abdominal pain may mimic such conditions as appendicitis or gallbladder problems. Chest pain may be mistaken for a heart attack.

• Blood pressure and heart rate may be elevated. The elevation of blood pressure can lead to one of the most severe complications. Redback spider • Life-threatening reactions are generally seen only in small children and the elderly. Widow spiders

Treatment • Pain management (Narcotics may be required for severe pain)

• Muscle relaxants

• Antivenom in severe cases

Black widow spider with egg case Australian funnel-web spiders

• Genera Atrax and Hadronyche • All are Australian except 1 species of Hadronyche from Chile Sydney funnel-web spider, • Produce atracotoxins- very Atrax robustus toxic to primates Australian funnel-web spiders

Symptoms of systemic envenoming include: • Tingling around the mouth and tongue • Facial muscle twitching • Nausea • Vomiting • Profuse sweating • Salivation • Shortness of breath. Sydney funnel-web spider Australian funnel-web spiders

Patients may rapidly develop: • Agitation • Confusion and coma associated with hypertension Sydney funnel-web spider • Metabolic acidosis • Dialation of the pupils • Generalized muscle twitching • Pulmonary edema. Australian funnel-web spiders

• Death results from progressive hypotension or possibly raised intracranial pressure resulting from cerebral edema • 13 deaths 1927-1980 from Hydronyche cerberea, A. robustus Southern tree funnel- web spider Australian funnel-web spiders

Treatment: – Supportive care – Applying a pressure immobilization bandage – Antivenom

H. infensa, Toowoomba funnel-web spider Mouse spiders

• Genus Missulena • Similar venom to Australian funnel-web spiders Brazilian wandering spider

• Genus Phoneutria • Found throughout Central and South America • Aggressive • In addition to neurotoxins, venom contains serotonin

Brazilian wandering spider

• Symptoms from mild envenomation – Pain – Edema – Hyperemia – Sweating

Brazilian wandering spider

• Symptoms from severe envenomation – Local pain – Tachycardia – Prostration – Profuse sweating – Poor peripheral profusion – Muscle fasciculation – Diarrhea – Vomiting – Priapism – Pulmonary edema

Brazilian wandering spider

• Treatment – Pain management – Supportive care – Antivenom – Mechanical ventilation • 2.3% of cases required antivenom in a series of 422 patients • Deaths from bites have been drastically reduced since introduction of antivenom in 1996

Recluse spiders

• Genus Loxosceles • Worldwide distribution, but most common in the new world • Venom contains the dermonecrotic agent sphingomyelinase D Brown recluse spider Recluse spiders

• Symptoms – Severe pain at bite site after about four hours

– Severe itching

– Nausea

– Vomiting Brown recluse spider – Fever

– Myalgias (muscle pain)

Recluse spiders

• Symptoms may progress to: – Blistering (common) – Necrosis (death) of skin and subcutaneous fat (less common) – Severe destructive necrotic lesions with deep wide Brown recluse spider bite borders (rare)

Recluse spiders

• First Aide – Apply ice to decrease pain and swelling.

– Elevate area if possible above the level of the heart.

– Wash the area thoroughly with cool water and mild soap.

– Avoid any strenuous activity because this can spread the spider's venom in Brown recluse spider bite the skin.

– Use acetaminophen for pain relief.

Recluse spiders

• Medical RX – Tetanus immunization

– Pain medication

– Antibiotics if signs of infection are present in the wound

– Antihistamines such as Brown recluse spider diphrenhydramine (Benadryl) for itch relief

Recluse spiders

• May form a necrotising ulcers that destroys soft tissue and may take months and very rarely years to heal, leaving deep scars • Damaged tissue may become gangrenous and eventually slough away Brown recluse spider bite Recluse spiders

• Systemic effects – Mild symptoms include nausea, vomiting, fever, rashes, and muscle and joint pain – Rarely more severe symptoms occur including

hemolysis, Brown recluse spider thrombocytopenia, and DIC Recluse spiders

• Treatment – Routine treatment should include elevation and immobilization of the affected limb, application of ice, local wound care, and tetanus prophylaxis – In almost all cases, bites are self-limited and typically heal Brown recluse spider without any medical intervention Recluse spiders

• An antivenom is available in South America • Chilean recluse-systemic reactions in 15% of cases and fatalities in 3-4%

Chilean recluse spider Six-eyed sand spider

• Genus Sicaritus • Found in southern hemisphere • Same family as recluse spiders (Sicariidae) • Considered by some as worlds most venomous spiders • Death and loss of limbs reported Other Spiders Causing Necrosis

• Hobo spider • Yellow sac spider

Hobo spider Yellow sac spider