ENVENOMING CAUSED BY BRAZILIAN SNAKES BENEDITO BARRAVIERA Full Professor of Tropical Diseases Botucatu Medical School - UNESP Research from The Center for the Study of Venoms and Venomous Animals – CEVAP São Paulo State University - UNESP - Brazil

MAIN BRAZILIAN SNAKES From Public Health point of view 1-Venomous snakes (about 58 species) Viperidae family – Bothrops sp (28 species) Crotalus sp (6 sub-species) Lachesis sp (2 species) Elapidae family – Micrurus sp (22 species) 2-Nonvenomous snakes (about 250 species) Boidae family - Boa constrictor, Eunectus murinus, Corallus caninus, Epicrates cenchria (11 species) Colubridae family – Clelia clelia, Liophis frenatus, Philodryas olfersii, Dipsas albifrons, Spilotis pullatus, Waglerophis merremii, Mastigodryas bifossatus, etc. (239 species)

MAIN BRAZILIAN VENOMOUS SNAKES Viperidae family – Bothrops sp – Bothrops jararaca, B. alternatus, B. moojeni, B. atrox (from Amazon region), B. cotiara, B. erytromelas, etc. -Responsible for 80 to 90% of accidents in Brazil -Crotalus sp – Crotalus durissus terrificus, C. d. collilineatus, C. d. marajoensis, C. d. cascavella, C. d. trigonicus, C. d. ruruima -Responsible for 10 to 20% of accidents in Brazil -Lachesis sp – Lachesis muta muta, Lachesis muta rhombeata -Responsible for 3% of accidents in the Amazon region - Brazil.

Bothrops jararaca Bothrops alternatus Bothrops moojeni Bothrops sp distribution

Bothrops moojeni

Crotalus sp distribution Crotalus durissus terrificus (South American rattlesnake)

Crotalus durissus terrificus

MAIN BRAZILIAN VENOMOUS SNAKES IN AMAZON REGION

MAIN BRAZILIAN VENOMOUS SNAKES IN THE AMAZON REGION Bothrops atrox * Bothrops brazili Bothriopsis bilineata Bothriopsis teniata Lachesis muta muta *

MAIN BRAZILIAN VENOMOUS SNAKES IN THE AMAZON REGION Lachesis muta muta Bothriopsis bilineata Bothrops atrox

Lachesis muta muta

MAIN BRAZILIAN VENOMOUS SNAKES Elapidae family -Micrurus sp – Micrurus frontalis, M. corallinus, M. paraensis, M. spixii, M. filiforms, etc. -Responsible for less than 1% of accidents in Brazil Micrurus corallinus

Micrurus sp distribution Micrurus frontalis

Boa constrictor Corallus caninus Eunectus murinus Boidae family Nonvenomous snakes

Colubridae family Nonvenomous snakes Spilotes pullatus Liophis miliaris Philodryas olfersii

Accidents caused by venomous animals in Brazil Snakes – 30,000/year Scorpions – 35,000/year Spiders – 19,500/year Bees and wasps – 1,500/year Catterpilars – 500/year São Paulo State – 2,000/year Botucatu – 100/year EPIDEMIOLOGY

Main season Summer – from December to March Patient´s characteristics Rural workers, Male (74.84%), 15 to 49 years old, lower limbs (62.75%) Snakes characteristics 87.33% Bothrops sp envenoming 7.43% Crotalus sp envenoming 1.37% Lachesis sp envenoming 0.41% Micrurus sp envenoming The Amazon region – 3,000 cases/year 90% Bothrops sp envenoming 10% Lachesis sp and others EPIDEMIOLOGY

Bothropic envenoming Clinical aspects Venom activity – Bothrops sp 1-Coagulative activity – cause bleeding and clotting disturbances Patient with severe gingival bleeding Bothrops alternatus

Mild bothropic envenomings Bothrops alternatus Bothropic envenoming Clinical aspects Venom activity – Bothrops sp 2-Citotoxic venom activity – citotoxicity - capacity to destroy tissues

Venom activity – Bothrops sp 2-Citotoxic venom activity – citotoxicity - capacity to destroy tissues Bothrops alternatus Moderate bothropic envenomings Bothropic envenoming Clinical aspects

Severe bothropic envenomings Bothrops alternatus Bothropic envenoming Clinical aspects Venom activity – Bothrops sp 2-Citotoxic venom activity – citotoxicity - capacity to destroy tissues

Venom activity – Bothrops sp 3-Hemorrhaging activity – spontaneous hemorrhage by damaging vascular endothelium Patients develop local or distant hemorrhage Bothrops alternatus Bothropic envenoming Clinical aspects

Venom activity – Crotalus sp 1-Neurotoxic activity – neurotoxic symptoms Crotalic envenoming Clinical aspects Crotalus durissus terrificus Midriasis Local bite Ptosis, Diplopia and blurred vision

Crotalic envenoming Clinical aspects Crotalus durissus terrificus Rhabdomyolysis Increase of CPK, DHL, AST and ALT enzymes Myoglobinuria Venom activity – Crotalus sp 2-Systemic rhabdomyolyses – skeletal muscle

Crotalic envenoming Clinical aspects Crotalus durissus terrificus Tubular necrosis causing renal failure Venom activity – Crotalus sp 3-Renal failure

Crotalic envenoming Clinical aspects Crotalus durissus terrificus Liver cells with mitochondrial edema Increase of Alanine aminotransferase enzyme Liver necrosis Venom activity – Crotalus sp 4-Liver toxicity Liver with edema

Lachetic envenoming Clinical aspects Venom activities – like Bothrops sp 1-Coagulative – cause bleeding and clotting disturbances 2-Citotoxic – citotoxicity - capacity to destroy tissues 3-Hemorrhaging – spontaneous hemorrhage by damaging vascular endothelium 4-Neurotoxic – bradicardia, diarrhea and arterial hipotension including shock

Elapidic envenoming Clinical aspects This venom - low molecular weight neurotoxins - neurotoxic facial expression (bilateral ptosis) - respiratory muscle paralysis. The most severe Brazilian ophidic accident! Micrurus corallinus Neurotoxic facial expression

MANAGEMENT OF THE SNAKEBITE “The early specialized medical assistance is essential to the evolution and prognosis of the patient” “All victims should be hospitalized and observed for at least 24 hours”

Tetanus immunoprophylaxis is recommended. Make the patient rest. If possible, wash the bite area with soap and water; Go to nearest hospital or medical facility as soon as possible where there is antivenom to be applied; Keep the bitten extremity above the level of the heart ; If possible, try to identify the snake and take it to the hospital; Tetanus immunoprophylaxis is recommended. What to DO immediately ?

No ice or any other type of cooling on the bite. Research has shown this to be potentially harmful; No tourniquets. This cuts blood flow completely and may result in loss of the affected limb; No electric shock. This method is under study and has yet to be proven effective. It could harm the victim; No incisions, no suction in the wound. Such measures have not been proven useful and may cause infection and persistent bleeding; Do not give beverages (alcohol or any other drink). What NOT to do

SPECIFIC ANTIVENOM TREATMENT Viperidae family Bothrops sp -Mild accident - 4 (100 mg) antibotropic venom ampules by intravenous route without allergic test; -Moderate accident - 8 (200 mg) antibotropic venom ampules by intravenous route without allergic test; -Severe accident - 12 (300 mg) antibotropic venom ampules by intravenous route without allergic test.

immunoprophylaxis. 1-Hospitalize the patient for at least 24 hours; 2-Make the Clotting Test after 12 hours to evaluate the clotting disturbance and indicate, if necessary, more antivenom; 3-Clean and wash the bite region; 4-Hydrate by intravenous route; 5-Give antibiotic prophylaxis with cefuroxime 125 to 250 mg twice a day; 6-Recommend tetanus immunoprophylaxis. SUPPORTIVE TREATMENT

SPECIFIC ANTIVENOM TREATMENT Viperidae family Crotalus sp -Mild accident - 10 (100 mg) anticrotalic venom ampules by intravenous route without allergic test; -Moderate accident - 20 (200 mg) anticrotalic venom ampules by intravenous route without allergic test; -Severe accident - 30 (300 mg) anticrotalic venom ampules by intravenous route without allergic test.

immunoprophylaxis; 7-If renal failure occurs hemodyalisis. 1-Hospitalize the patient for at least 24 hours; 2-Make Clotting Test after 12 hours to evaluate clotting disturbance and indicate, if necessary, more antivenom; 3-Clean and wash the bite region; 4-Hidrate to prevent renal failure with Manitol 20%, four times a day for at least 5 days. 5-Increase pH with Sodium bicarbonate 5%, 50 ml by oral route, four times a day. 5-Give antibiotic prophylaxis – cefuroxime 125 to 250 mg twice a day, for 5 to 7 days; 6-Indicate tetanus immunoprophylaxis; 7-If renal failure occurs hemodyalisis. SUPPORTIVE TREATMENT

SPECIFIC ANTIVENOM TREATMENT Viperidae family Lachesis sp Apply 10 to 20 antilachetic or antibotropic/lachetic venom ampules by intravenous route without allergic test; Supportive treatment = Bothrops sp; These accidents the Amazon region.

SPECIFIC ANTIVENOM TREATMENT Elapidade family Micrurus sp Apply 10 (150 mg) antielapidic venom ampules by intravenous route without allergic test; Supportive treatment to prevent neurotoxic effects Respiratory paralysis Atropine, neostigmine and edrophonium chloride are indicated. Less than 1% of accidents occur in Brazil every year.

Prevention of Antivenom Reactions according to Health Ministry -Pre-medication - 10 to 15 minutes before antivenom treatment; -Dextroclorfeniramine (Polaramine®) – 0.08 or Prometazine (Fenergan®) – 0.6 mg/Kg mg/Kg by intramuscular route; -Hidrocortisone (Solu-cortef®) – 10 mg/Kg by intravenous route;

Prevention of Antivenom Reactions according to Health Ministry - Cimetidine (Tagamet®) – 10 mg/Kg or Ranitidine (Antak®) – 2 mg/Kg by intravenous route -Antivenom, without dilution, for 15 to 30 minutes, by intravenous route without allergic test; “Medical supervision must be continuous during antivenom administration”

NONVENOMOUS SNAKE ACCIDENTS Boidae family No envenomation Wash the bite area with soap and water; Inform the patient that antivenom treatment is not necessary. Accident with Boa constrictor

NONVENOMOUS SNAKE ACCIDENTS Colubridae family -Rare envenomation; -Rare pain and local swelling; -Rare partial defibrination; -Controversial antibotropic treatment. Envenomation by Philodryas olfersii

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