Bothrops atrox, the most important snake involved in human envenomings in the amazon: How venomics contributes to the knowledge of snake biology and clinical toxinology

Abstract

Bothrops atrox snakes are mostly endemic of the Amazon rainforest and is certainly the South American pit viper responsible for most of the snakebites in the region. The composition of B. atrox venom is significantly known and has been used to trace the relevance of the venom phenotype for snake biology and for the impacts in the clinics of human patients involved in accidents by B. atrox. However, in spite of the wide distribution and the great medical relevance of B. atrox snakes, B. atrox taxonomy is not fully resolved and the impacts of the lack of taxonomic resolution on the studies focused on venom or envenoming are currently unknown. B. atrox venom presents different degrees of compositional variability and is generally coagulotoxic, inducing systemic hematological disturbances and local tissue damage in snakebite patients. Antivenoms are the effective therapy for attenuating the clinical signs. This review brings a comprehensive discussion of the literature concerning B. atrox snakes encompassing from snake taxonomy, diet and venom composition, towards clinical aspects of snakebite patients and efficacy of the antivenoms. This discussion is highly supported by the contributions that venomics and antivenomics added for the advancement of knowledge of B. atrox snakes, their venoms and the treatment of accidents they evoke.

Keywords: Antivenom; Antivenomics; Common lancehead; Envenoming; Pit viper; Snakebite; Venomics; Viperidae.

Fig. 1

Seasonal characteristics of 612 Bothrops atrox specimens causing envenomations in Manaus, Western Brazilian Amazon. Above) Frequency of B. atrox responsible for snakebites brought seasonally to the hospital, separated by size and sex. Colors show the rainiest (blue) and driest (red) trimesters of the year. The specimens were grouped by age as follows: neonate males and females (snout-vent length, SVL<300 mm), juvenile males (SVL between 300 and 470 mm) and juvenile females (SVL between 300 and 850 mm), adult males (SVL>470 mm) and adult females (SVL>850 mm) according to Silva et al. (2017). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 2

Bothrops atrox specimens resting or foraging in different substrates. A-D pictures show adult specimens on the ground: A) ambush hunting in a forest environment; B) resting in an urban place, between a wall and a container for water storage. C) moving in a forest environment on a small body of water. D) moving on the leaf-litter. E-G pictures show juvenile specimens in ambush hunting on different aerial substrates. Photos: Paulo S. Bernarde.

Fig. 3

Proportion of prey found in the diet of Bothrops atrox specimens from the region of Manaus, according to sizes. The stomach content was analyzed in 612 specimens of B. atrox snakes brought to the health service by the envenomed patients and classified according to the reproductive stage classified as described in Fig. 1: A) Adults, B) Juveniles, C) Neonates.

Fig. 4

Prey of Bothrops atrox, according to literature records (Bernarde and Abe, 2010, Bisneto and Kaefer, 2019, Macedo-Bernarde and Bernarde, 2005, Martins and Gordo, 1993, Martins and Oliveira, 1998, Nascimento et al., 2008). A-K pictures represent preys associated to neonate or juvenile specimens of B. atrox. A) Centipede climbing a tree trunk; B-D) pictures of anurans (Leptodactylus fuscus, Adenomera andreae, Pristimantis fenestratus, respectively), preys of neonate or juvenile specimens of B. atrox; E) A tropical house gecko (Hemidactylus mabouia, an exotic species) preyed on by a juvenile B. atrox; F and G) Two species of lizards (Kentropyx pelviceps and Ameiva ameiva, respectively), preys of all ontogenetic stages of B. atrox; H–K) Epictia tenella, Leptodeira annulata, Tantilla melanocephala and Imantodes cenchoa, respectively, preys of neonate or juvenile B. atrox; L) Taraba major, a prey rarely reported for B. atrox; M-P) Rodents on the forest ground. Taxonomic identification of rodents is rarely permorfed in snake dietary studies. Photos: A = Rafael Marllus Negreiros de Almeida; B – K and M - P = Paulo S. Bernarde; L = Vanderley Pereira dos Santos.

Fig. 5

Local tissue damage in B. atrox envenoming. A) schematic presentation of the intense inflammatory process in local of B. atrox snakebites. B) presence of polymorphonuclear cells with phagocytic action and cytoplasmic vacuoles in blister exudates. C) picture demonstrating intense cell migration and detachment of the upper layer of the skin in sample biopsy after blister formation, resulting from the inflammatory process in B. atrox envenoming.

Fig. 6

Local manifestations from Bothrops atrox envenomings. A and B) Extensive edema in lower limb of two male patients; picture A also shows local bleeding. C) Edema, secondary infection and necrosis in fingers of the right hand of a female patient. D) Edema, secondary infection and an extensive necrotic plaque in the external side of the left foot of a female patient. E) Extensive edema, ecchymosis and blister with bloody content in the left foot of a male patient. F) An impressive necrotic area, with tissue exposure, in the right lower limb of a male patient. G) A necrotic plaque in the toe of the right foot of a male patient. H) Compartment syndrome across the left lower limb extension, post-fasciotomy. Photos: A, C, D, G and H = Lisele Brasileiro; B, E and F = Ageane Mota da Silva.

Fig. 7

Hemorrhagic manifestations from Bothrops atrox envenomings. A) macroscopic hematuria; B) presence of erythrocytes in urine, observed by optic microscopy; C) conjunctival bleeding; D) ecchymosis in the whole upper limb in a patient bitten in the hand; E) brain presenting hypodense lesion in the right frontal lobe and edema in cortical-subcortical, and perilesional areas on a CT scan. Photos: A, B, C and D = Lisele Brasileiro; E = Aline Pérez-Gómes.

Fig. 8

Sequelae from Bothrops atrox envenomings. A) Chronic lymphedema in an elder male patient, after 5 years of envenomation, with extensive edema and skin thickening accompanied by pain, parestesia and itching in the left lower limb (A.1); A.2 shows a radiological image of the affected limb. B) Left hand presenting claw-like positioning of fingers with permanent atrophy and stiffness of the 1st, 2nd and 3rd fingers after 3 years of envenomation; physical examination reveals atrophy, paresthesia and immobility (B.1); hand radiography showing permanent structural alterations (B.2). C) young female presenting a reddish skin and scaring after several years of envenomation at the bitten site; D) leg aspect after 4 months of extensive skin grafting secondary to compartmental syndrome in and young adult – patient presented with extensive necrotic areas after delayed access to proper health care; E) young male presenting scarring secondary to surgical incision as management of compartment syndrome secondary to snakebite F) leg aspect after 3 years of snakebite in the left leg – delayed access to proper care lead to extensive muscular, nerve and skin tissue excision, which resulted in atrophy as patient got older; leg is not functional and patient currently waits for amputation surgery. Photos: A and B = Iran Mendonça da Silva; C = Guilherme Salazar; D = Fernando Val and Jacqueline Sachett; E and F = Altair Seabra de Farias.