Snake eyes: Characterization of topical ocular exposures from rattlesnakes in Arizona.

Patients occasionally present with reports of ocular exposure to fluids from rattlesnakes, claiming or suspecting the substance to be venom. This study set out to evaluate and characterize reported cases of suspected venom-induced ophthalmia in humans. A retrospective review of rattlesnake exposures reported to the Arizona Poison and Drug Information Center over a 24-year period was conducted for ocular exposures. Recorded information included patient demographics, clinical course, laboratory results, and treatments. Documentation regarding interactions between patients and snakes was reviewed by Arizona Poison and Drug Information Center herpetologists to evaluate what substance was expelled from the snake resulting in ocular exposure. Our review of rattlesnake encounters found a total of 26 ocular exposure cases. Patient demographics were largely intentional interactions and involved the male sex. Symptoms ranged from asymptomatic to minor effects with 46.2% managed from home and treated with fluid irrigation. A review of cases by herpetologists concluded the exposure patients commonly experienced was to snake musk. Kinematics of venom expulsion by rattlesnakes conclude the venom gland must be compressed, fangs erected to ≥60o, and fang sheath compressed against the roof of the mouth for venom expulsion. Evidence suggests the chance of venom "spitting" by rattlesnakes is close to zero. Rattlesnakes are documented to forcefully expel airborne malodorous "musk" defensively. An important distinction to remember is musk has a foul odor and is usually colorless, while venom is comparatively odorless and yellow. Rattlesnake venom-induced ophthalmia is a rare event as venom expulsion requires the kinematics of feeding or defensive bites. If the rattlesnake is not in the process of biting or otherwise contacting some other object with its mouth, it is more biologically plausible patients are being exposed to snake musk as a deterrent. Whether it's venom or musk, topical exposure to the eyes should prompt immediate irrigation.

Fashionably late: A characterization of late coagulopathies in rattlesnake envenomations between Fab and F(ab')2 antivenoms.

BACKGROUND: Rattlesnake envenomation may lead to a multitude of clinical effects, including a late onset hemorrhage. Laboratory values such as platelets and fibrinogen are commonly used to assess the risk of developing a life-threatening bleed. To date, no specific threshold has been identified that links a lab value to the risk of bleeding. This has led to widespread practice variability among clinicians managing snake bites. In assessing risk for patients, we apply the concept that the more abnormal the lab values are, the higher the risk probably is. Late onset coagulopathies pose a unique clinical challenge because they indicate the potential risk for a life-threatening hemorrhage, yet they have been identified after hospital discharge. There are currently two antivenom (AV) products on the US market to treat rattlesnake envenomations, a Fab product, CroFab® (BTG, UK) and a F (ab')2 product, Anavip® (Bioclon, Mexico). OBJECTIVE: This study intended to characterize the incidence and severity of late coagulopathies reported to a Regional Poison Center (RPC) and hypothesized that late coagulopathies occur at rates higher than previously reported in the literature. Additionally, we sought to compare rates of late coagulopathy between Fab and F (ab')2 AV. METHODS: The investigators performed an in-depth review of all suspected snakebite envenomations from 2018 to 2020 that presented to an Arizona healthcare facility in the RPC's catchment area between January 2018 through December of 2020. Patients were excluded from analysis if they did not receive any antivenom, had an incomplete medical record with the APDIC, were diagnosed as something other than a rattlesnake bite or had a known medical history that clouded the diagnosis or assessment of a rattlesnake envenomation. RESULTS: In total, 522 records were reviewed of which 283 patients met the inclusion criteria. There were 149 patients who received Fab AV and 134 who received F (ab')2. No significant baseline or demographic differences existed between the groups. 95 of the 283 patients developed a late onset coagulopathy. 39% of the late onset coagulopathies were delayed, 32% were recurrent and 29% were persistent. When comparing the two different AV products, delayed or recurrent coagulopathies occurred in 36% of Fab AV- and 10% of F (ab')2 treated patients. Persistent coagulopathies occurred in 17% of Fab AV- and 8% of F (ab')2 treated patients. Interestingly, there were zero cases of late hypofibrinogenemia in any of the 134 F (ab')2 treated patients compared to 26% of all Fab treated ones. The average onset of late coagulopathy post-bite was 8 days for Fab AV and 7 for F (ab')2. CONCLUSION: The results from this study suggest the total rate of late onset coagulopathies may be underestimated. Additionally, our results suggest the potential that F (ab')2 AV may be associated with fewer late onset coagulopathies, especially late onset hypofibrinogenemia.

Mohave Rattlesnake (Crotalus scutulatus) Identification Revisited.

Crotalus scutulatus (Mohave rattlesnake) is a clinically significant pit viper broadly distributed across much of the arid southwestern United States and mainland Mexico. Identification of C scutulatus is a concern among emergency medical service and emergency department personnel owing to its reputation for severe envenomations and difficulty in visually differentiating between C scutulatus and other species, primarily Crotalus atrox (western diamond-backed rattlesnake). We contrast distinctive characteristics of C scutulatus, C atrox, and 3 other sympatric species: Crotalus molossus, Crotalus ornatus, and Crotalus viridis (western and eastern black-tailed rattlesnakes and prairie rattlesnake, respectively). Greenish coloration eliminates C atrox but does not confirm C scutulatus. Obvious coarse and fine speckling of the dorsal pattern and a pale postocular stripe intersecting the mouth characterize C atrox. Dorsal speckling is insignificant or absent in the other species, whereas the pale postocular stripe passes above the mouth in C scutulatus and C viridis and is absent in C molossus and C ornatus. Tails boldly ringed with alternating black and white or contrasting shades of gray are shared by C atrox and C scutulatus, respectively, but a lack of boldly ringed tails characterizes the other species. The proximal rattle segment is yellow and black, or entirely yellow, in C scutulatus but black in the others. The most reliable visual identifications are based on evaluations of multiple traits, all of which are variable to some extent. Traits such as tail ring width and the size and number of crown scales have frequently been overemphasized in the past.

When one phenotype is not enough: divergent evolutionary trajectories govern venom variation in a widespread rattlesnake species.

Understanding the origin and maintenance of phenotypic variation, particularly across a continuous spatial distribution, represents a key challenge in evolutionary biology. For this, animal venoms represent ideal study systems: they are complex, variable, yet easily quantifiable molecular phenotypes with a clear function. Rattlesnakes display tremendous variation in their venom composition, mostly through strongly dichotomous venom strategies, which may even coexist within a single species. Here, through dense, widespread population-level sampling of the Mojave rattlesnake, Crotalus scutulatus, we show that genomic structural variation at multiple loci underlies extreme geographical variation in venom composition, which is maintained despite extensive gene flow. Unexpectedly, neither diet composition nor neutral population structure explain venom variation. Instead, venom divergence is strongly correlated with environmental conditions. Individual toxin genes correlate with distinct environmental factors, suggesting that different selective pressures can act on individual loci independently of their co-expression patterns or genomic proximity. Our results challenge common assumptions about diet composition as the key selective driver of snake venom evolution and emphasize how the interplay between genomic architecture and local-scale spatial heterogeneity in selective pressures may facilitate the retention of adaptive functional polymorphisms across a continuous space.

Interfang Distances of Rattlesnakes: Sexual, Interspecific, and Body Size-related Variation, and Implications for Snakebite Research and Management.

OBJECTIVES: Snakebite severity corresponds to size of snake because the amount of venom a snake injects is positively associated with snake size. Because fang marks are often present on snakebite patients, we tested whether the relationship between snake length and distance between fang puncture wounds can be generalized for rattlesnakes of genus Crotalus. METHODS: We measured 2 interfang distances from 79 rattlesnakes of both sexes, 5 species, and varying body length: 1) distance between fang bases in anesthetized snakes, and 2) distance between fang punctures in a membrane-covered beaker bitten defensively. RESULTS: Statistical analyses supported our 2 hypotheses, that 1) body size-related fang divergence during fang protraction (ie, anterolateral movement during fang erection), and 2) the relationship between snake length and interfang distance are similar between the sexes and among different rattlesnake species. We therefore derived a general equation to estimate snake length based on distance between fang marks, and recommended 5 snake size categories: very small (<10 mm), small (10-15 mm), medium (15-20 mm), large (20-25 mm), and very large (>25 mm). CONCLUSIONS: The distance between fang marks on a snakebite patient may be used to estimate the size or size category of the offending snake, which in some cases may have predictive value for overall clinical severity of a given envenomation. Assessing interfang distance from puncture wounds can improve snakebite research and anticipation of snakebite severity.

Recognizing dangerous snakes in the United States and Canada: a novel 3-step identification method.

The rapid and accurate recognition of dangerously venomous snakes following bites is crucial to making appropriate decisions regarding first aid, evacuation, and treatment. Past recommendations for identification of dangerous North American pit vipers have often required subjective determinations of head shape or relied on traits shared with some nondangerous species (elliptical pupils and undivided subcaudal scales). Heat-sensitive facial pits are diagnostic but require close examination of the dangerous head, and cephalic traits are useless when working with a decapitated carcass. Exclusive of cephalic traits, pit vipers north of Mexico can be recognized by the combination of keeled middorsal scales and undivided subcaudal scales. The order of colored rings is usually suggested to identify coral snakes in the United States, yet extension of the colored rings across the ventral scales must be added as an essential identifying factor to ensure elimination of all harmless look-alikes. A novel 3-step flow chart is presented that allows dangerous snakes in the United States and Canada to be recognized quickly and dependably without relying on cephalic traits. This process cannot be used in other countries, however, due to greater variability of these characteristics in snakes from other parts of the world. Finally, close examination of potentially venomous snakes is extraordinarily dangerous and steps to safeguard those making such observations are discussed.

Pressure immobilization delays mortality and increases intracompartmental pressure after artificial intramuscular rattlesnake envenomation in a porcine model.

STUDY OBJECTIVES: We determine the effect of pressure immobilization on mortality and intracompartmental pressure after artificial intramuscular Crotalus atrox envenomation in a porcine model. METHODS: We prospectively studied 20 pigs using a randomized, controlled design. After anesthesia, C atrox venom (20 mg/kg) was injected with a 22-gauge needle 10 mm deep into the tibialis anterior muscle of the hind leg. Pigs were randomized to receive either pressure immobilization (applied 1 minute after envenomation and maintained throughout the duration of the experiment) or no pressure immobilization. We measured time to death, intracompartmental pressure before venom injection and at 2 hours after injection, and leg circumference at a standardized location before injection and immediately postmortem. Duration of survival was compared using Kaplan-Meier survival analysis. RESULTS: The dose of venom resulted in 100% mortality. The median survival was longer in the pressure immobilization group (191 minutes, range 140 to 240 minutes) than in the control group (median 155 minutes, range 119 to 187 minutes). The difference between the groups was 36 minutes (95% confidence interval [CI] 2 to 64 minutes; P =.0122). The mean intracompartmental pressures were 67+/-13 mm Hg+/-SD with pressure immobilization and 24+/-5 mm Hg without pressure immobilization. The difference between groups was 43 mm Hg (95% CI 32 to 53 mm Hg). The mean circumferences were 14.3 cm in the pressure immobilization group and 19.1 cm in the control group. The difference between groups was -4.8 cm (95% CI -5.7 to -3.9 cm). CONCLUSION: Compared with control animals without treatment, the pressure immobilization group had longer survival, less swelling, and higher intracompartmental pressures after artificial, intramuscular C atrox envenomation in our porcine model.

Mojave toxin in venom of Crotalus helleri (Southern Pacific Rattlesnake): molecular and geographic characterization.

Mojave toxin (MT) was detected in five of 25 Crotalus helleri (Southern Pacific rattlesnake) sampled using anti-MT antibodies and nucleotide sequence analysis. All of the venoms that were positive for MT were collected from Mt San Jacinto in Riverside Co., California. Since this population is geographically isolated from C. scutulatus scutulatus (Mojave rattlesnake), it is unlikely that this finding is due to recent hybridization. MT concentration differences between C. helleri and C. s. scutulatus reflected the presence of 'isoforms' of the toxin in the venom. Whereas C. s. scutulatus generally has several isoforms of the toxin (detected by Western blotting), only one 'isoform' that focused at pI 5.1 was detected in C. helleri. Both acidic and basic subunits of MT sequences were obtained from C. helleri DNA with primers specific for MT, but only from snakes that had MT in their venom. The sequence identity of the C. helleri acidic subunit to the C. s. scutulatus subunit was 84.9%, whereas the sequence identity of the C. helleri basic subunit was 97% to the C. s. scutulatus basic subunit. Using casein, fibrin, and hide powder azure as substrates, assays for proteolytic activity suggested that C. helleri possesses several different types of metalloproteinases in their venom. However, proteolytic activity was not detected, or present in reduced amounts, in specimens having MT. Clinical neurotoxicity following envenomation by certain populations of C. helleri may be due to MT.

Crotalidae polyvalent immune Fab (ovine) antivenom is efficacious for envenomations by Southern Pacific rattlesnakes (Crotalus helleri).

STUDY OBJECTIVE: Southern Pacific rattlesnake (Crotalus helleri ) venom is not 1 of the 4 venoms used to produce Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV). There is currently no published clinical experience regarding the efficacy of this new antivenom for confirmed C helleri envenomation, and animal data suggest greatly diminished efficacy. We assessed the efficacy of FabAV for patients with confirmed C helleri envenomation. METHODS: We conducted a prospective observational study of 23 consecutive rattlesnake envenomations that were treated with FabAV at our center. Patients were excluded if the species of snake could not be confirmed, if FabAV antivenom was not given, or if Antivenin (Crotalidae) polyvalent (equine) was given. We collected serial physical examination and laboratory data over a 24-hour period to serially evaluate the severity score and performed follow-up to evaluate delayed reactions. RESULTS: There were 15 patients who received FabAV and had the species of rattlesnake confirmed (9 C helleri, 4 C scutulatus scutulatus, 1 C mitchellii pyrrhus, 1 C ruber ruber ). C helleri envenomations demonstrated similar improvement in serial snakebite severity scores to those of other species. Three patients treated with scheduled dosing had recurrence of progressive swelling (2 C helleri and 1 C mitchellii pyrrhus ) during the 24-hour study period. CONCLUSION: We observed similar improvement in FabAV-treated patients with C helleri envenomation compared with those of other species and conclude that this treatment in standard doses appears efficacious for bites by this species. Progressive swelling may recur despite scheduled dosing.