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Poisonous & scrub typhus mite

Dr. Sangob Sanit Department of Parasitology, Faculty of Medicine, Chiang Mai University, THAILAND • Identify important morphological characteristics of arthropods of medical importance • Describe clinical signs & symptoms caused by / of the arthropods & treatments & prevention • Describe morphology, lifecycle & medical importance of Scrub typhus mite https://www.facebook.com/ToxicAnt.org - เพราะทุกสิ่งล้วนเป็นพิษ Four categories of poisonous arthropods

1. : spiders, centipedes 2. Stinging: , , 3. Contact: caterpillars, moths & butterflies, rove beetles, millipedes 4. Eating: blister beetles, horseshoe crabs Biting: spiders, centipedes Poisonous spiders

 Latrodectus mactans (Southern black widow spider)  Latrodectus geometricus (Brown widow spider); Thailand  Latrodectus elegans (Black widow spider); Thailand  Loxosceles reclusa (Brown recluse spider)  Loxosceles rufescens (Mediterranean recluse spider) ; Thailand  Atrax robustus (Sydney funnel web spider) Spiders • Both male & female have 1 pairs of Fangs or claws chelicerae tipped with fangs or claws.

venomous glands Venomous glands open at the end of fangs

The spider venom is a toxic cocktail produced mainly for feeding & protection purposes. 1. Latrodectus mactans (Southern black widow spider) -แมงมุมแม่ม่ายดา Adult Female -shiny black with ventral red hourglass marking -size ~ 3.75 to 5 cm including leg span; bodies ~1.25 cm Male - size 0.6 cm - lack the characteristic hourglass, may have red spotting on the top/ underside of the abdominal segment ♀ ♂

https://entnemdept.ufl.edu/creatures/urban/spiders/black_widow_spider.htm Egg sac - beige-colored egg sac (⌀ 1.0-1.25 cm) - 1 egg sac contains ~ 220 eggs - produce ~ 10 egg sacs in a lifetime

https://spiderid.com/picture/1903/ https://entnemdept.ufl.edu/creatures/urban/spiders/black_widow_spider.htm 9 Habitat

Outdoor: wood, rock piles, rodent burrows , hollow tree stumps Indoor: outhouses, garages, sheds, and basements (D'Amour et al. 1936)

https://usaspiders.com/latrodectus-mactans-southern-black-widow/ 10 Black widow venom

Latrodectism is caused by the bite of a female black widow spider Neurotoxin: alpha- (α-LTX),

release acetylcholine & norepinephrine at nerve terminals

muscle cramping & systemic effects (pain, muscle rigidity, vomiting & sweating)

minor effects major effects (death rate ; 4%-5% in untreated cases) Flushing & bite site with surrounding erythema https://doi.org/10.1080/23120053.2018.1453271 symptoms /examination

. Bite site: Target lesion with local redness & pain, sometimes bite site cannot be seen. - pain at the site increases, spreads, reaching a maximum within 1-3 hr, and later subsides . Prominent muscle cramping & pain most notably of abdominal, back, & leg muscles, starting locally & then progressing diffusely. . Tachycardia, hypertension . Diaphoresis . Nausea/vomiting . Symptoms may wax & wane, but generally disappear over 2-3 days . Can cause cardiac failure & respiratory collapse in children 12 23,409 cases (2000-2008; USA):

- 65% minor clinical effects - 33.5% moderate effects (longer duration of symptoms, treatment required) - 1.4% with major effects (life-threatening)

- 9872 cases minor effects; - dermal irritation (58.7%) - erythema (28.6%) - pain (17.9%) - edema (13.6%) - abdominal pain (9.7%)

https://pubmed.ncbi.nlm.nih.gov/22116992/ 13 Treatment

■ Local care ■ Tetanus prophylaxis ■ Symptomatic treatment is the mainstay of therapy. - Opioid analgesia - Benzodiazepines to reduce muscle spasm - Antihypertensives as needed (nitroprusside = agent of choice)

■ Black widow antivenom is indicate if severe symptoms or high-risk patient . - Children & elderly patients -Severe pain despite symptomatic treatment -Severe envenomation (seizures, uncontrolled HTN, respiratory failure) -Significant comorbidities (HTN, atherosclerotic disease) -Pregnancy

■ Antivenom is derive from horse serum; therefore, administer a test dose frst; risk immediately & serum sickness at 7-10 days.

First Aid for the Boards Third Edition 3rd Edition by Barbara Blok, Dickson Cheung , Timothy Platts-Mills, p 723 14 2. Latrodectus geometricus (Brown widow spider) -แมงมุมแม่ม่ายสีน้าตาล • Female 10 mm > Male • Light to medium brown with ventral orange hourglass marking • Not aggressive & rarely has been recorded biting humans

https://www.pinterest.de/pin/435160382735731597/ ventral orange hourglass marking https://www.expatgo.com/my/2016/01/11/dangerous-critters-malaysia-know/ https://cisr.ucr.edu/invasive-species/brown-widow-spider Egg sac - tan, spherical, spiky - 1 egg sac contains ~ eggs - produce ~ 20 egg sacs in a lifetime https://doi.org/10.1186/s40409-015-0010-2

Thailand: 18 provinces Nan Lampang Phrae Nakhon Ratchasima Khon Kaen Si Sa Ket Buri Ram Ubon Ratchathani Bangkok Nakhon Prathom Phetchabun Phitsanulok Chon Buri Chachoengsao Kanchanaburi Prachuap Khiri Khan Ratchaburi Surat Thani รายงานผลงานวิจัยประจ าปี ๒๕๖๐ สานักวิจัยพัฒนาการอารักขาพืช :http://doa.go.th/research/attachment.php?aid=2707 Brown widow venom

Neurotoxin: alpha-latrotoxin (α-LTX)

~ 15% of bites  no venom injected

Symptoms: - muscle pain & cramps - abdominal pain & cramps - weakness in legs & difficulty in walking - pain in regional lymph nodes & raised temperature Area of pain & erythema (white arrow); 6 x 3.5 cm

Earwood, Ryan C et al. “A Case of Brown Widow Envenomation in Central Florida.” Cureus vol. 12,7 e9165. 13 Jul. 2020, doi:10.7759/cureus.9165 19 Treatment

. Local wound care & tetanus prophylaxis . Diazepam orally for muscle relaxation . Hydromorphone IV for pain control . Diphenhydramine for itching . Promethazine for nausea

Earwood, Ryan C et al. “A Case of Brown Widow Envenomation in Central Florida.” Cureus vol. 12,7 e9165. 13 Jul. 2020, doi:10.7759/cureus.9165 Severe reaction from envenomation by the brown widow spider, Latrodectus geometricus (Araneae: Theridiidae) doi: 10.1097/SMJ.0b013e31817f4d89 20 3. Latrodectus elegans (black widow spider) -แมงมุมแม่ม่ายหลังเพลิง Adult: - Shiny black with ventral blood-red hourglass marking ; a vertical black-line in the middle of the hourglass marking - black with bright blood-red pattern on dorsum

Egg sac

https://www.youtube.com/watch?v=ZkG5gyHjQkQ 21 Thailand: 7 provinces

Khon Kaen Ubon Ratchathani Phitsanulok Chai Nat Chon Buri Chachoengsao Prachuap Khiri Khan Lop Buri

Habitat: cassava plantation, borders between forest & cassava plantation

ผลงานวิจัยเต็มเรื่อง การประชุมวิชาการ อารักขาพืช แห่งชาติครั้งที่ 14 หน้าที่ 63-77 https://issuu.com/ppc14th/docs/1?fbclid=IwAR1U_1wPYSggtdUbFpDFdhxauvNYjUcjmahbZdt8pUTrPulhkDaGFGCy_-k 4. Loxosceles reclusa (Brown recluse spider/ violin spiders) -แมงมุมสันโดษสีน้า ตาล • Not aggressive & nocturnal habits • Female 7-12 mm > Male • Tan to dark brown with darked violin-shaped pattern on front half of head region, violin spiders • Six eyes arranged in 3 pairs (dyads) 3 pairs of dyads

violin-shaped pattern Brown recluse spider venom Venom contains a variety of cytotoxic enzymes

Sphingomyelinase D

enzyme that breaks down sphingomyelin in plasma membranes

cell destruction

inflammation

Local necrotic lesions, systemic (rarely) Clinical course of cutaneous :

(a) Lesion with ecchymoses & areas of pallor 26 h after the bite; the patient received specific antivenom & corticosteroids; (b) Lesion with ecchymoses, pallor, & blisters 8 days after the bite. (c) Necrotic eschar 29 days after the bite; (d) Ulcerated lesion 35 days after the bite, which required reconstructive plastic surgery

P. Gopalakrishnakone, Gerardo A. Corzo, Elia Diego-Garcia,Maria Elena de Lima. Spider .p 425 25 Treatment

. Supportive therapy as needed. . Local wound care & tetanus prophylaxis. . An antivenom is not available in Thailand. . Nitroglycerin, phentolamine, heparin, hyperbaric O2, cyproheptadine, & have all been used but show no clear evidence for efficacy. . Dapsone (a leukocyte esterase inhibitor) is still recommended in some texts, but has limited benefit & is aassociated with hemolysis (in patients with G6PD) an methemoglobinemia. . Delayed (not early) excision, debridement, and possible skin grafting

First Aid for the Emergency Medicine Boards Third Edition 3rd Edition by Barbara Blok, Dickson Cheung , Timothy Platts-Mills, p 724 26 4. Loxosceles rufescens (Mediterranean recluse spider) - แมงมุมสันโดษเมดิเตอร์เรเนียน 28 Nentwing w et al., 2017 5. Atrax robustus (Sydney funnel web spider) -แมงมุมใยกรวยซิดนีย์ • Female 1-4 cm, Male 1-3 cm • Black, glossy carapace covering the front part of the body • Highly aggressive when provoked • Highly toxic to humans & can cause severe envenomation symptoms Distribution maps of Australian spiders.

(a) Funnel-web spiders (Atrax spp., Hadronyche spp., and Illawarra wisharti) (b) redback spider (Latrodectus hasselti), (c) mouse spiders (Missulena spp.), (d) Australian tarantulas (Theraphosidae)

P. Gopalakrishnakone, Gerardo A. Corzo, Elia Diego-Garcia,Maria Elena de Lima. Spider Venoms.p 425 31 Atrax robustus venom

-Atracotoxin (robustoxin): neurotoxin that causes repetitive firing & prolonged action potentials; continuous release of acetylcholine; can lead to circulatory & respiratory failure

32 Symptoms: rapid onset 0.5 -2 hrs

• Sweating, tingling around the mouth & tongue, salivation, watery eyes • Elevated heart rate, elevated blood pressure, nausea, vomiting, shortness of breath (caused by airway obstruction), agitation, confusion • Muscle spasms, pulmonary edema, metabolic acidosis Treatment

First-aid treatment; cleansing the area with soap and tap water, then immediately applying a pressure immobilization bandage -This technique limits the spread of the venom throughout the body & minimizes the area affected by the bite

Emergency medical treatment should be sought as soon as possible.

Antivenom should be given at the earliest sign of systemic envenomation. (patient should be connected to appropriate cardiorespiratory monitoring, while a supply of antivenom )

https://www.ncbi.nlm.nih.gov/books/NBK535394/ 34 https://www.youtube.com/watch?v=h84VIVfxmv0

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35 Latrodectus mactans ?

36 Biting: centipedes Centipedes

• Order Chilopoda (Body length 2-30 cm) • Family:Scolopendridae (16-25 cm) • Thailand: Scolopendra subspinipes (~ 23 cm) S. dehaani S. morsitans etc.

The centipede genus Scolopendra in mainland Southeast Asia: molecular phylogenetics, geometric morphometrics and external morphology as tools for species delimitation. PLoS One. 2015;10(8):e0135355–37. CENTIPEDES

• Flattened head • Forcipules /claws  modified first pair of legs rather than true mouthparts • Venom glands Medical importance

• injury resulting from forcipules (claws) pierce skin & inject venom into wound • Wound  paired hemorrhagic marks • Centipede's venom  pain & swelling in the area of the bite • Not life-threatening to humans  children & allergic reactions Symptoms:

• Severe pain, swelling & redness • Skin necrosis, swollen, painful lymph nodes in the regions of the bitten limb, headache, palpitations or a racing pulse, nausea and vomiting, local itching & burning sensations • A severe bite from a large centipede on a child, senior or person with a weakened heart can cause heart attack if untreated (exceptionally rare). Centipedes bite lesion

งูไทยทั่วราชอาณาจักร - Snakes of Thailand (~อาณาจักรงูไทยในแดนสยาม~) https://www.facebook.com/groups/908415245857501/about Treatment:

• Rinsing with cold water/ice on the bite site • Apply papain (found in papaya) on the bite site  deactivate the majority of the centipede venom's proteins • Painkillers, non-steroidal anti-inflammatory , & anti-anxiety medications • Antibiotics (infected/necrotic) • Check for muscle tissue breakdown (urine test) and/or an EKG (heart & vascular problems) Emergency Department cases centipede bite

Prevelance of centipede envenomation by year from 2006–2015. 44 45 46 Stinging: Scorpions, bees, & Scorpions

• Class: Arachnida

• Order: Scorpionida viviparous • 1,500 species: Desert, Tropic, Arctic

• 25 dangerous species: genus Centruroides, Bruthacus, Buthus Thailand: Scorpions

Family: Buthidae Family: Scorpionidae

Lychas mucronatus Heterometrus spinifer

https://www.thailandnatureproject.com/scorpiones---scorpions.html 49 • Venoms - neurotoxins - lipid neurotransmitters - serotonin - enzymes Venom Symptoms: • Painful but rarely life-threatening • Numbness, tingling & swelling around sting site

• Systemic venom effects may include: - Difficulty breathing - Muscle twitching/thrashing - Unusual head, neck & eye movements - Drooling - Sweating - Nausea & vomiting - Hypertension - Tachycardia/arrhythmia - Restlessness/excitability/inconsolable crying Treatment:

• Clean sting area with antiseptic & apply ice • Supportive treatment • Anascorp (antivenom-centruroides ) Bees

Apis dorsata (ผึ้งหลวง) Apis florea (ผึ้งมิ้ม) Apis andreniformis (ผึ้งม้าน) Apis cerana (ผึ้งโพรง) Apis mellifera (ผึ้งพันธุ์)

(Rattanawannee A & Chanchao C,2011) The members of the colony

Female (longer abdomen) -no organs for collecting -have a

Male Female -doesn’t have a stinger (atrophic reproductive system) -no organs for collecting pollen -have a stinger -fertilize the queen (age>12 days) Bee sting •2 Lancet • Acid gland, alkaline gland or Dofour’s gland Bee venom: - (50-60%) - Phospholipase A2 (10-12%) - Phospholipase B - - Secapin - - Dopamine - Nor-adrenaline Carpena M. et al. 2020; doi:10.3390/nu12113360 Melittin: - pain - induces minor allergic reactions - membrane-disrupting material; causes tissue damage - cardiotoxin - increases capillary blood flow & cell permeability - triggers lysis of red blood cells - enhances the spread of

Phospholipase A2: lung congestion & allergic reactions

-

57 Symptoms:

Mild reaction The majority of bee sting symptoms are very mild and do not require medical attention. • a sharp, burning pain • an area of raised, red skin • slight itchiness • Slight swelling around the sting area • In most people, the swelling & pain go away within a few hours https://beehivehero.com/bee-sting-symptoms/ Moderate reaction - stronger response to bee venom; large local reaction (LLR)

• Severe redness around the sting which may gradually increase in size to a diameter of 10 cm/more over a period of 24–48 hours

• 5-10% a person experiences a LLR, ▶ they will develop a systemic allergic reaction to a sting in the future.

https://www.medicalnewstoday.com/articles/322075#are-they-common Severe allergic reaction • A severe allergic reaction (anaphylaxis) to bee stings is potentially life-threatening & requires emergency treatment.

• Signs & symptoms include: - Skin reactions, itching & flushed / pale skin - Difficulty breathing - Swelling of throat & tongue - Weak, rapid pulse - Nausea, vomiting / diarrhea - Dizziness / fainting - Loss of consciousness angioedema

 People who have a severe allergic reaction to a bee sting have a 25% to 65% chance of anaphylaxis the next time they're stung. Multiple bee stings

- Get stung more than a dozen times, accumulation of venom may induce toxic reaction

Signs and symptoms include: Nausea, vomiting or diarrhea, headache, vertigo, convulsions, fever, dizziness or fainting

Dead Treatment:

• Remove any immediately (credit card)

• Don't pinch the stinger  inject more venom

• Wash the site with soap & water. • Apply ice to the site  20 minutes once every hour

• Oral  diphenhydramine (Benadryl) / non sedating one such as loratadine (Claritin)

• Apply hydrocortisone cream / antihistamine cream  relieve redness, itching & swelling Treatment: continued

• Acetaminophen (Tylenol) / ibuprofen (Motrin)  pain relief

• Tetanus booster  If it's been more than 10 years since the last booster

Treatment: Anaphylactic attack Anaphylactic attack • Epinephrine (adrenaline)  reduce allergic response • Oxygen • Intravenous (IV) antihistamines & cortisone  reduce inflammation of air passages & improve breathing • A beta agonist (such as albuterol)  relieve breathing symptoms • Cardiopulmonary resuscitation (CPR)  stop breathing or heart stops beating. Prevention • Remove hives and nests near your home by a professional

• Always carry two prescribed epinephrine injectors (Adrenaclick, Auvi-Q, EpiPen, Symjepi) for an allergic reaction if you are allergic and use it as directed Prevention • Take care when drinking sweet beverages & fruits outside • Wear close-toed shoes when walking outside. Don't wear bright colors / floral prints & loose clothing • Avoid perfumed soap & shampoo • When driving, keep your windows rolled up • Be careful when mowing the lawn / trimming vegetation, activities that might arouse in a or wasp nest Wasp & Hornet

https://www.crittercontroltriangle.com/north-carolina-hornets-wasps-bees-yellow-jackets/ Thailand:

ต้อม คนทามาหากิน https://www.facebook.co m/470614116796945/vid Vespa affinis Vespa tropica eos/4308143145909972 (ต่อหัวเสือ) (ต่อหลุม) Prapenpuksiri, R. et al. (2016). Comparative proteomic analysis of two wasps venom, Vespa tropica and Vespa affinis. Toxicon. 119. 10.1016/j.toxicon.2016.06.005. 69 (Vespa mandarinia)

Nesting Habits of Some Hornet Species (, Vespidae) in Northern Thailand https://www.thaiscience.info/Article%20for%20ThaiScience/Article/5/10002939.pdf 70 Vespa mandarinia

นักล่าต่อหลุม Thanaphol jaipanya https://www.youtube.com/watch?v=ZmpNtwNMJNI 71 Medical importance

Stinger • Multiple stinging • Renal failure • Toxins: Phospholipase A & B, wasp kinin, hyaluronidase, MCDP (mast cell degranulating peptide), Histamine, serotonin, dopamine, nor-adrenaline

 Kinins: hemolysis & pain  Phospholipase A1: allergic reactions.  Mastoparans: destroy mast cells Vespid venoms:

- cause contraction of smooth muscles - reduced blood pressure - release of histamine & other biogenic amines

- lytic peptides & phospholipases induce hemolysis ▶ kidney damage -Phospholipase A1 ▶ allergic reactions -Mastoparans ▶ destroy mast cells Sting site: -immediate pain -local swelling -erythema

Bullous reaction Pain & itching: - immediate pain caused by a vespid sting is principally due to serotonin & kinins - pain ◀ nerotonin, , tyramine, & catecholamines - pain often continues for several hours - itching at the sting site may persist for several days Treatment: • As treatments of bee stinging • > 30 stings - admit, observe, give supportive treatment • Dialysis – reduce renal failure Eating: Blister beetles & Horseshoe crabs Blister beetles

ด้วงน ้ามันเสือเหลือง ด้วงไฟเดือนห้า ด้วงน ้ามันเหลืองด าใหญ่ (M. cichorii) (Mylabris phalerata)

Medical importance

• Cantharidin (poisonous chemical)  severe damage to gastrointestinal & urinary tracts 1 blister beetle  cantharid (~5-7 mg)  5-10 adults  potentially lethal to human  (0.5-1 mg cantharidin/kg) stable & remains toxic in dead beetles for a  long time

Symptoms:

• Severity; ranging from temporary to reduced digestive ability to death (depends on the amount of cantharidin ingested and the size and health of each person) • Symptoms - appear within hours & include irritation & inflammation of the digestive & urinary tract - Irritation may also result in secondary infection & bleeding - Calcium levels may be drastically lowered & heart muscle tissue can be damaged  death Treatment:

• No specific antidote for cantharidin toxicosis - cantharadin removal, reduction & immediate symptomatic therapy

• Prevention is the most effective way to avoid cantharidin toxicosis. Eating : Horseshoe crabs

edible inedible

Tachypleus gigas Carcinoscorpius rotundicauda Coastal horseshoe crab Mangrove horseshoe crab (แมงดาจาน) (แมงดาถ้วย,เหรา) 30-40 cm X 25 cm 20-25 cm X 15 cm

Tail shape Tail shape Medical importance

Horseshoe crab eggs;Tetrodotoxin (TTX) [potent neurotoxin, sodium channel blocker]

TTX-producing bacteria / Plangton accumulated TTX in Horseshoe crab Horseshoe crab Symptoms:

Symptoms typically develop within 30 mins to 4 hrs of ingestion. • Stage 1 Perioral & lingual numbness / paresthesia, nausea, vomiting • Stage 2 Numbness progresses markedly, motor paralysis of extremities • Stage 3 Progressive motor paralysis, bulbar muscle paralysis, Patient is conscious • Stage 4 Pespiratory failure, hypoxia, unconsciousness and hypotension may occur, fixed and dilated pupils (Kanchanapongkul 2008) (Kanchanapongkul 2008) Treatment: • Supportive treatment based on symptoms, with aggressive early airway management.

• Empty stomach; feed activated charcoal to bind toxin

• Alpha adrenergic agonists + intravenous fluids to combat hypotension

• No antidote developed but monoclonal antibody specific to tetrodotoxin was effective in tests on mice. Chigger mite, Scrub typhus mite

Larva ** Chigger ** - very small size (200x400 um) - round or oval shape - orange - red color - 3 pairs of legs - hairy - scutum at dorsum Leptotrombidium spp. Morphology

Adult : - small size (1-2 mm long) - oval or eight shape - reddish - 4 pairs of legs - hairy Life cycle of Leptotrombidium spp. Medical importance

 Vector of scrub typhus : Orientia tsutsugamushi (previously Rickettsia tsutsugamushi)

 Maculopapular rash & Eschar Annual Epidemiology Surveillance Report 2017; Department of Disease Control,Thailand Annual Epidemiology Surveillance Report 2017; Department of Disease Control,Thailand Signs & symptoms: • Incubation period (6-20 days) • Chigger bite (often painless and unnotices), maculopapular rash & eschar • High fever (“intermittent” 39.5-40 oC), headache, difficulty in breathing, abdominal pain, nausea & vomiting, lymphadenopathy • Severe cases can develop encephalitis and pneumonia may be fatal Treatment: • Doxycycline • Tetracycline • Chloramphenicol • Rifampicin