The Experts below are selected from a list of 3528 Experts worldwide ranked by ideXlab platform
Geoffrey K Isbister - One of the best experts on this subject based on the ideXlab platform.
-
In Vitro Neurotoxicity of Chinese Krait (Bungarus multicinctus) Venom and Neutralization by Antivenoms.
Toxins, 2021Co-Authors: Qing Liang, Geoffrey K Isbister, Tam Minh Huynh, Wayne C. HodgsonAbstract:Bungarus multicinctus, the Chinese krait, is a highly venomous elapid Snake which causes considerable morbidity and mortality in southern China. B. multicinctus venom contains pre-synaptic PLA2 neurotoxins (i.e., β-bungarotoxins) and post-synaptic neurotoxins (i.e., α-bungarotoxins). We examined the in vitro neurotoxicity of B. multicinctus venom, and the efficacy of specific monovalent Chinese B. multicinctus Antivenom, and Australian polyvalent elapid Snake Antivenom, against venom-induced neurotoxicity. B. multicinctus venom (1-10 μg/mL) abolished indirect twitches in the chick biventer cervicis nerve-muscle preparation as well as attenuating contractile responses to exogenous ACh and CCh, but not KCl. This indicates a post-synaptic neurotoxic action but myotoxicity was not evident. Given that post-synaptic α-neurotoxins have a more rapid onset than pre-synaptic neurotoxins, the activity of the latter in the whole venom will be masked. The prior addition of Chinese B. multicinctus Antivenom (12 U/mL) or Australian polyvalent Snake Antivenom (15 U/mL), markedly attenuated the neurotoxic actions of B. multicinctus venom (3 μg/mL) and prevented the inhibition of contractile responses to ACh and CCh. The addition of B. multicinctus Antivenom (60 U/mL), or Australian polyvalent Snake Antivenom (50 U/mL), at the t90 time point after the addition of B. multicinctus venom (3 μg/mL), did not restore the twitch height over 180 min. The earlier addition of B. multicinctus Antivenom (60 U/mL), at the t20 or t50 time points, also failed to prevent the neurotoxic effects of the venom but did delay the time to abolish twitches based on a comparison of t90 values. Repeated washing of the preparation with physiological salt solution, commencing at the t20 time point, failed to reverse the neurotoxic effects of venom or delay the time to abolish twitches. This study showed that B. multicinctus venom displays marked in vitro neurotoxicity in a skeletal muscle preparation which is not reversed by Antivenom. This does not appear to be related to Antivenom efficacy, but due to the irreversible/pseudo-irreversible nature of the neurotoxins.
-
An Examination of the Neutralization of In Vitro Toxicity of Chinese Cobra (Naja atra) Venom by Different Antivenoms.
Biomedicines, 2020Co-Authors: Qing Liang, Geoffrey K Isbister, Tam Minh Huynh, Nicki Konstantakopoulos, Wayne C. HodgsonAbstract:The Chinese Cobra (Naja atra) is an elapid Snake of major medical importance in southern China. We describe the in vitro neurotoxic, myotoxic, and cytotoxic effects of N. atra venom, as well as examining the efficacy of three Chinese monovalent Antivenoms (N. atra Antivenom, Gloydius brevicaudus Antivenom and Deinagkistrodon acutus Antivenom) and an Australian polyvalent Snake Antivenom. In the chick biventer cervicis nerve-muscle preparation, N. atra venom (1-10 µg/mL) abolished indirect twitches in a concentration-dependent manner, as well as abolishing contractile responses to exogenous acetylcholine chloride (ACh) and carbamylcholine chloride (CCh), indicative of post-synaptic neurotoxicity. Contractile responses to potassium chloride (KCl) were also significantly inhibited by venom indicating myotoxicity. The prior addition of Chinese N. atra Antivenom (0.75 U/mL) or Australian polyvalent Snake Antivenom (3 U/mL), markedly attenuated the neurotoxic actions of venom (3 µg/mL) and prevented the inhibition of contractile responses to ACh, CCh, and KCl. The addition of Chinese Antivenom (0.75 U/mL) or Australian polyvalent Antivenom (3 U/mL) at the t90 time point after the addition of venom (3 µg/mL), partially reversed the inhibition of twitches and significantly reversed the venom-induced inhibition of responses to ACh and CCh, but had no significant effect on the response to KCl. Venom (30 µg/mL) also abolished direct twitches in the chick biventer cervicis nerve-muscle preparation and caused a significant increase in baseline tension, further indicative of myotoxicity. N. atra Antivenom (4 U/mL) prevented the myotoxic effects of venom (30 µg/mL). However, G. brevicaudus Antivenom (24 U/mL), D. acutus Antivenom (8 U/mL) and Australian polyvalent Snake Antivenom (33 U/mL) were unable to prevent venom (30 µg/mL) induced myotoxicity. In the L6 rat skeletal muscle myoblast cell line, N. atra venom caused concentration-dependent inhibition of cell viability, with a half maximal inhibitory concentration (IC50) of 2.8 ± 0.48 μg/mL. N. atra Antivenom significantly attenuated the cytotoxic effect of the venom, whereas Australian polyvalent Snake Antivenom was less effective but still attenuated the cytotoxic effects at lower venom concentrations. Neither G. brevicaudus Antivenom or D. acutus Antivenom were able to prevent the cytotoxicity. This study indicates that Chinese N. atra monovalent Antivenom is efficacious against the neurotoxic, myotoxic and cytotoxic effects of N. atra venom but the clinical effectiveness of the Antivenom is likely to be diminished, even if given early after envenoming. The use of Chinese viper Antivenoms (i.e., G. brevicaudus and D. acutus Antivenoms) in cases of envenoming by the Chinese cobra is not supported by the results of the current study.
-
Severe rhabdomyolysis from red-bellied black Snake (Pseudechis porphyriacus) envenoming despite Antivenom.
Toxicon : official journal of the International Society on Toxinology, 2016Co-Authors: Adeline Y.l. Lim, Puneet N. Singh, Geoffrey K IsbisterAbstract:Envenoming by the Australian red-bellied black Snake (Pseudechis porphyriacus) causes non-specific systemic symptoms, anticoagulant coagulopathy, myotoxicity and local effects. Current management for systemic envenoming includes administration of one vial of tiger Snake Antivenom within 6 h of the bite to prevent myotoxicity. We present a case of severe rhabdomyolysis in a 16 year old male which developed despite early administration of one vial of tiger Snake Antivenom. Free venom was detected after the administration of Antivenom concurrent with rapidly decreasing Antivenom concentrations. The case suggests that insufficient Antivenom was administered and the use of larger doses of Antivenom need to be explored for red-bellied black Snake envenoming.
-
Clinical features of serum sickness after Australian Snake Antivenom.
Toxicon : official journal of the International Society on Toxinology, 2015Co-Authors: Nicole M. Ryan, Michael A. Downes, Geoffrey K IsbisterAbstract:Serum sickness is a delayed immune reaction in which the immune system responds to a protein in antiserum as a potentially harmful substance and mounts an IgG-mediated antibody response. A 32 year-old female patient had systemic envenoming following a bite by a red-bellied black Snake (Pseudechis porphyriacus). She was treated with Tiger Snake Antivenom and recovered over 24 h and did not develop myotoxicity. She then presented with local pain, itching and swelling, which was partially treated with antihistamines. Eleven days after the bite she presented again with symptoms of worsening serum sickness including rash on the upper legs, joint and muscle pain in arms, ankles and knees, and nausea. The patient was prescribed five days of prednisone 50 mg/day, antihistamine 10 mg/day and analgesia 1000 mg/day and improved over 2 days. She had no further problems on follow up at 4 months. This case highlights that serum sickness can cause significant effects after the treatment of Snake envenoming. It develops 5-14 days after Antivenom administration and has characteristic clinical and laboratory features. Severe cases of serum sickness can result in morbidity but it appears to respond well to corticosteroid treatment.
-
Incidence of serum sickness after the administration of Australian Snake Antivenom (ASP-22).
Clinical toxicology (Philadelphia Pa.), 2015Co-Authors: Nicole M. Ryan, Simon G A Brown, Renai T Kearney, Geoffrey K IsbisterAbstract:AbstractContext: Serum sickness is a delayed immune reaction resulting from the injection of foreign protein or serum. Antivenom is known to cause serum sickness but the incidence and characteristics are poorly defined. Objective: To investigate the incidence and clinical features of serum sickness following the administration of Australian Snake Antivenoms. Materials and methods: This was a prospective cohort study of patients recruited to the Australian Snakebite Project who received Snake Antivenom from November 2012 to March 2014. Demographics, clinical information, laboratory tests and Antivenom treatment were recorded prospectively. Patients administered Antivenom were followed up at 7–10 days and 6 weeks’ post-Antivenom. The primary outcome was the proportion with serum sickness, pre-defined as three or more of: fever, erythematous rash/urticaria, myalgia/arthralgia, headache, malaise, nausea/vomiting 5–20 days post-Antivenom. Results: During the 16-month period, 138 patients received Antivenom. 23...
Wayne C. Hodgson - One of the best experts on this subject based on the ideXlab platform.
-
In Vitro Neurotoxicity of Chinese Krait (Bungarus multicinctus) Venom and Neutralization by Antivenoms.
Toxins, 2021Co-Authors: Qing Liang, Geoffrey K Isbister, Tam Minh Huynh, Wayne C. HodgsonAbstract:Bungarus multicinctus, the Chinese krait, is a highly venomous elapid Snake which causes considerable morbidity and mortality in southern China. B. multicinctus venom contains pre-synaptic PLA2 neurotoxins (i.e., β-bungarotoxins) and post-synaptic neurotoxins (i.e., α-bungarotoxins). We examined the in vitro neurotoxicity of B. multicinctus venom, and the efficacy of specific monovalent Chinese B. multicinctus Antivenom, and Australian polyvalent elapid Snake Antivenom, against venom-induced neurotoxicity. B. multicinctus venom (1-10 μg/mL) abolished indirect twitches in the chick biventer cervicis nerve-muscle preparation as well as attenuating contractile responses to exogenous ACh and CCh, but not KCl. This indicates a post-synaptic neurotoxic action but myotoxicity was not evident. Given that post-synaptic α-neurotoxins have a more rapid onset than pre-synaptic neurotoxins, the activity of the latter in the whole venom will be masked. The prior addition of Chinese B. multicinctus Antivenom (12 U/mL) or Australian polyvalent Snake Antivenom (15 U/mL), markedly attenuated the neurotoxic actions of B. multicinctus venom (3 μg/mL) and prevented the inhibition of contractile responses to ACh and CCh. The addition of B. multicinctus Antivenom (60 U/mL), or Australian polyvalent Snake Antivenom (50 U/mL), at the t90 time point after the addition of B. multicinctus venom (3 μg/mL), did not restore the twitch height over 180 min. The earlier addition of B. multicinctus Antivenom (60 U/mL), at the t20 or t50 time points, also failed to prevent the neurotoxic effects of the venom but did delay the time to abolish twitches based on a comparison of t90 values. Repeated washing of the preparation with physiological salt solution, commencing at the t20 time point, failed to reverse the neurotoxic effects of venom or delay the time to abolish twitches. This study showed that B. multicinctus venom displays marked in vitro neurotoxicity in a skeletal muscle preparation which is not reversed by Antivenom. This does not appear to be related to Antivenom efficacy, but due to the irreversible/pseudo-irreversible nature of the neurotoxins.
-
An Examination of the Neutralization of In Vitro Toxicity of Chinese Cobra (Naja atra) Venom by Different Antivenoms.
Biomedicines, 2020Co-Authors: Qing Liang, Geoffrey K Isbister, Tam Minh Huynh, Nicki Konstantakopoulos, Wayne C. HodgsonAbstract:The Chinese Cobra (Naja atra) is an elapid Snake of major medical importance in southern China. We describe the in vitro neurotoxic, myotoxic, and cytotoxic effects of N. atra venom, as well as examining the efficacy of three Chinese monovalent Antivenoms (N. atra Antivenom, Gloydius brevicaudus Antivenom and Deinagkistrodon acutus Antivenom) and an Australian polyvalent Snake Antivenom. In the chick biventer cervicis nerve-muscle preparation, N. atra venom (1-10 µg/mL) abolished indirect twitches in a concentration-dependent manner, as well as abolishing contractile responses to exogenous acetylcholine chloride (ACh) and carbamylcholine chloride (CCh), indicative of post-synaptic neurotoxicity. Contractile responses to potassium chloride (KCl) were also significantly inhibited by venom indicating myotoxicity. The prior addition of Chinese N. atra Antivenom (0.75 U/mL) or Australian polyvalent Snake Antivenom (3 U/mL), markedly attenuated the neurotoxic actions of venom (3 µg/mL) and prevented the inhibition of contractile responses to ACh, CCh, and KCl. The addition of Chinese Antivenom (0.75 U/mL) or Australian polyvalent Antivenom (3 U/mL) at the t90 time point after the addition of venom (3 µg/mL), partially reversed the inhibition of twitches and significantly reversed the venom-induced inhibition of responses to ACh and CCh, but had no significant effect on the response to KCl. Venom (30 µg/mL) also abolished direct twitches in the chick biventer cervicis nerve-muscle preparation and caused a significant increase in baseline tension, further indicative of myotoxicity. N. atra Antivenom (4 U/mL) prevented the myotoxic effects of venom (30 µg/mL). However, G. brevicaudus Antivenom (24 U/mL), D. acutus Antivenom (8 U/mL) and Australian polyvalent Snake Antivenom (33 U/mL) were unable to prevent venom (30 µg/mL) induced myotoxicity. In the L6 rat skeletal muscle myoblast cell line, N. atra venom caused concentration-dependent inhibition of cell viability, with a half maximal inhibitory concentration (IC50) of 2.8 ± 0.48 μg/mL. N. atra Antivenom significantly attenuated the cytotoxic effect of the venom, whereas Australian polyvalent Snake Antivenom was less effective but still attenuated the cytotoxic effects at lower venom concentrations. Neither G. brevicaudus Antivenom or D. acutus Antivenom were able to prevent the cytotoxicity. This study indicates that Chinese N. atra monovalent Antivenom is efficacious against the neurotoxic, myotoxic and cytotoxic effects of N. atra venom but the clinical effectiveness of the Antivenom is likely to be diminished, even if given early after envenoming. The use of Chinese viper Antivenoms (i.e., G. brevicaudus and D. acutus Antivenoms) in cases of envenoming by the Chinese cobra is not supported by the results of the current study.
-
Cross-neutralisation of the neurotoxic effects of Egyptian cobra venom with commercial tiger Snake Antivenom
Basic & clinical pharmacology & toxicology, 2012Co-Authors: Rachelle Kornhauser, Peter Mirtschin, Geoffrey K Isbister, Margaret A. O'leary, Nathan Dunstan, Wayne C. HodgsonAbstract:Cross-neutralisation has been demonstrated for haemorrhagic venoms including Echis spp. and Cerastes spp. and for Australia elapid procoagulant toxins. A previous study showed that commercial tiger Snake Antivenom (TSAV) was able to neutralise the systemic effects of the Egyptian cobra, Naja haje, in vivo but it is unclear if this was true cross-neutralisation. The aim of the current study was to determine whether TSAV can neutralise the in vitro neurotoxic effects of N. haje venom. Both Notechis scutatus (10 μg/ml) and N. haje (10 μg/ml) venoms caused inhibition of indirect (supramaximal V, 0.1 Hz, 0.2 msec.) twitches of the chick biventer cervicis nerve–muscle preparation with t90 values (i.e. the time to produce 90% inhibition of the original twitch height) of 26 ± 1 min. (n = 4) and 36 ± 4 min.; (n = 4). This effect at 10 μg/ml was significantly attenuated by the prior addition of TSAV (5 U/ml). A comparison of the reverse-phase HPLC profiles of both venoms showed some similarities with peak elution times, and SDS-PAGE analysis elucidated comparable bands across both venoms. Further analysis using Western immunoblotting indicated TSAV was able to detect N. haje venom, and enzyme immunoassay showed that in-house biotinylated polyclonal monovalent N. scutatus antibodies were able to detect N. haje venom. These findings demonstrate cross-neutralisation between different and geographically separated Snakes supporting potential immunological similarities in Snake toxin groups for a large range of Snakes. This provides more evidence that Antivenoms could be developed against specific toxin groups to cover a large range of Snakes.
-
Isolation and pharmacological characterisation of papuantoxin-1, a postsynaptic neurotoxin from the venom of the Papuan black Snake (Pseudechis papuanus).
Biochemical pharmacology, 2005Co-Authors: Sanjaya Kuruppu, Shane Reeve, A. Ian Smith, Wayne C. HodgsonAbstract:The Papuan black Snake (Pseudechis papuanus) is found throughout the southern coastal regions of Papua New Guinea and is thought to occur in the adjacent region of Iriyan Jaya. Neurotoxicity is a major symptom of envenomation by this species. This study describes the isolation of the first neurotoxin papuantoxin-1 from the venom of P. papuanus. Papuantoxin-1 (6738Da), which accounts for approximately 5% of the whole venom, was purified to homogeneity using successive steps of RP-HPLC. The toxin (0.3-1.0 microM) caused concentration dependent inhibition of indirect twitches (0.1 Hz, 0.2 ms and supramaximal V) and inhibited the responses to nicotinic agonists in the chick biventer cervicis nerve-muscle preparation, indicating a postsynaptic mode of action. However, papuantoxin-1 displayed no signs of myotoxicity. Papuantoxin-1 displayed pseudo-irreversible antagonism of cumulative concentration-response curves to carbachol at the skeletal muscle nicotinic receptors with an estimated pA2 value of 6.9+/-0.3. CSL black Snake Antivenom, which is raised against the venom of the Australian black Snake Pseudechis australis, appears to be effective in reversing the effects of papuantoxin-1. Thus, black Snake Antivenom should be considered for the treatment of the neurotoxic effects following envenomation by the Papaun black Snake.
-
Neurotoxic effects of venoms from seven species of australasian black Snakes (Pseudechis): Efficacy of black and tiger Snake Antivenoms
Clinical and experimental pharmacology & physiology, 2005Co-Authors: Sharmaine Ramasamy, Bryan G. Fry, Wayne C. HodgsonAbstract:SUMMARY 1. Pseudechis species (black Snakes) are among the most widespread venomous Snakes in Australia. Despite this, very little is known about the potency of their venoms or the efficacy of the Antivenoms used to treat systemic envenomation by these Snakes. The present study investigated the in vitro neurotoxicity of venoms from seven Australasian Pseudechis species and determined the efficacy of black and tiger Snake Antivenoms against this activity. 2. All venoms (10 µg/mL) significantly inhibited indirect twitches of the chick biventer cervicis nerve–muscle preparation and responses to exogenous acetylcholine (ACh; 1 mmol/L), but not to KCl (40 mmol/L), indicating activity at post-synaptic nicotinic receptors on the skeletal muscle. 3. Prior administration of either black or tiger Snake Antivenom (5 U/mL) prevented the inhibitory effects of all Pseudechis venoms. 4. Black Snake Antivenom (5 U/mL) added at t90 (i.e. the time-point at which the original twitch height was reduced by 90%) significantly reversed the effects of P. butleri (28 ± 5%), P. guttatus (25 ± 8%) and P. porphyriacus (28 ± 10%) venoms. Tiger Snake Antivenom (5 U/mL) added at the t90 time-point significantly reversed the neurotoxic effects of P. guttatus (51 ± 4%), P. papuanus (47 ± 5%) and P. porphyriacus (20 ± 7%) venoms. 5. We show, for the first time, the presence of neurotoxins in the venom of these related Snake species and that this activity is differentially affected by either black Snake or tiger Snake Antivenoms.
Nicholas A Buckley - One of the best experts on this subject based on the ideXlab platform.
-
Population pharmacokinetics of an Indian F(ab')2 Snake Antivenom in patients with Russell's Viper (Daboia russelii) bites
PLoS neglected tropical diseases, 2015Co-Authors: Geoffrey K Isbister, Kalana Maduwage, Nicholas A Buckley, Ana Saiao, Shaluka Jayamanne, Shahmy Seyed, Fahim Mohamed, Umesh Chathuranga, Alexandre Mendes, Chandana AbeysingheAbstract:Background There is limited information on Antivenom pharmacokinetics. This study aimed to investigate the pharmacokinetics of an Indian Snake Antivenom in humans with Russell’s viper bites.
-
Snake Antivenom for Snake venom induced consumption coagulopathy
Cochrane Database of Systematic Reviews, 2015Co-Authors: Kalana Maduwage, Nicholas A Buckley, Janaka H De Silva, David G Lalloo, Geoffrey K IsbisterAbstract:Background Snake venom induced consumption coagulopathy is a major systemic effect of envenoming. Observational studies suggest that Antivenom improves outcomes for venom induced consumption coagulopathy in some Snakebites and not others. However, the effectiveness of Snake Antivenom in all cases of venom induced consumption coagulopathy is controversial. Objectives To assess the effect of Snake Antivenom as a treatment for venom induced consumption coagulopathy in people with Snake bite. Search methods The search was done on 30 January 2015. We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (OvidSP), three other sources, clinical trials registers, and we also screened reference lists. Selection criteria All completed, published or unpublished, randomised, controlled trials with a placebo or no treatment arm, where Snake Antivenom was administered for venom induced consumption coagulopathy in humans with Snake bites. Data collection and analysis Two authors reviewed the identified trials and independently applied the selection criteria. Main results No studies met the inclusion criteria for this review. Authors' conclusions Randomised placebo-controlled trials are required to investigate the effectiveness of Snake Antivenom for clinically relevant outcomes in patients with venom induced consumption coagulopathy resulting from Snake bite. Although ethically difficult, the routine administration of a treatment that has a significant risk of anaphylaxis cannot continue without strong evidence of benefit.
-
The Cochrane Library - Snake Antivenom for Snake venom induced consumption coagulopathy
The Cochrane database of systematic reviews, 2015Co-Authors: Kalana Maduwage, Nicholas A Buckley, David G Lalloo, H. Janaka De Silva, Geoffrey K IsbisterAbstract:Background Snake venom induced consumption coagulopathy is a major systemic effect of envenoming. Observational studies suggest that Antivenom improves outcomes for venom induced consumption coagulopathy in some Snakebites and not others. However, the effectiveness of Snake Antivenom in all cases of venom induced consumption coagulopathy is controversial. Objectives To assess the effect of Snake Antivenom as a treatment for venom induced consumption coagulopathy in people with Snake bite. Search methods The search was done on 30 January 2015. We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (OvidSP), three other sources, clinical trials registers, and we also screened reference lists. Selection criteria All completed, published or unpublished, randomised, controlled trials with a placebo or no treatment arm, where Snake Antivenom was administered for venom induced consumption coagulopathy in humans with Snake bites. Data collection and analysis Two authors reviewed the identified trials and independently applied the selection criteria. Main results No studies met the inclusion criteria for this review. Authors' conclusions Randomised placebo-controlled trials are required to investigate the effectiveness of Snake Antivenom for clinically relevant outcomes in patients with venom induced consumption coagulopathy resulting from Snake bite. Although ethically difficult, the routine administration of a treatment that has a significant risk of anaphylaxis cannot continue without strong evidence of benefit.
-
Clinical effects of red-bellied black Snake (Pseudechis porphyriacus) envenoming and correlation with venom concentrations: Australian Snakebite Project (ASP-11)
The Medical Journal of Australia, 2010Co-Authors: Andrew Churchman, Simon G A Brown, Margaret A. O'leary, Nicholas A Buckley, Alan S Tankel, Chris Gavaghan, Colin B. Page, Anna Holdgate, Geoffrey K IsbisterAbstract:Objective: To describe the clinical features and laboratory findings in patients with definite red-bellied black Snake (RBBS; Pseudechis porphyriacus) bites, including correlation with results of venom assays. Design, patients and setting: Prospective cohort study of patients with definite RBBS bites, recruited to the Australian Snakebite Project from January 2002 to June 2010. Main outcome measures: Clinical and laboratory features of envenoming; peak venom concentrations and Antivenom treatment. Results: There were 81 definite RBBS bites; systemic envenoming occurred in 57 patients (70%) and local envenoming alone occurred in one patient. Systemic envenoming was characterised by local envenoming in 55 patients (96%), systemic symptoms in 54 patients (95%), anticoagulant coagulopathy with a raised activated partial thromboplastin time (aPTT) in 35 patients (61%) and myotoxicity in seven patients (12%). One patient required non-invasive ventilation for severe myotoxicity that resulted in muscle weakness. Three patients developed local ulceration. There were no deaths. Twenty-two envenomed patients (39%) received tiger Snake or black Snake Antivenom, and administration within 6 hours of the bite was associated with normalisation of the aPTT. Eight patients (36%) had immediate hypersensitivity reactions to Antivenom, including one case of anaphylaxis. The median peak venom concentration in 37 systemically envenomed patients with serum available was 19 ng/mL (interquartile range, 12–50 ng/mL; range, 3–360 ng/mL), which did not correlate with clinical severity. In 17 patients who received Antivenom and had venom concentration measured, no venom was detected in serum after the first Antivenom dose, including nine who were given one vial of tiger Snake Antivenom. Conclusion: RBBS envenoming caused local effects, systemic symptoms, anticoagulant coagulopathy and, uncommonly, myotoxicity. One vial of tiger Snake or black Snake Antivenom appears to be sufficient to remove venom and neutralise reversible effects, but
-
Clinical effects of red-bellied black Snake (Pseudechis porphyriacus) envenoming and correlation with venom concentrations: Australian Snakebite Project (ASP-11).
The Medical journal of Australia, 2010Co-Authors: Andrew Churchman, Simon G A Brown, Margaret A. O'leary, Nicholas A Buckley, Chris Gavaghan, Colin B. Page, Anna Holdgate, Alan Tankel, Geoffrey K IsbisterAbstract:To describe the clinical features and laboratory findings in patients with definite red-bellied black Snake (RBBS; Pseudechis porphyriacus) bites, including correlation with results of venom assays. Prospective cohort study of patients with definite RBBS bites, recruited to the Australian Snakebite Project from January 2002 to June 2010. Clinical and laboratory features of envenoming; peak venom concentrations and Antivenom treatment. There were 81 definite RBBS bites; systemic envenoming occurred in 57 patients (70%) and local envenoming alone occurred in one patient. Systemic envenoming was characterised by local envenoming in 55 patients (96%), systemic symptoms in 54 patients (95%), anticoagulant coagulopathy with a raised activated partial thromboplastin time (aPTT) in 35 patients (61%) and myotoxicity in seven patients (12%). One patient required non-invasive ventilation for severe myotoxicity that resulted in muscle weakness. Three patients developed local ulceration. There were no deaths. Twenty-two envenomed patients (39%) received tiger Snake or black Snake Antivenom, and administration within 6 hours of the bite was associated with normalisation of the aPTT. Eight patients (36%) had immediate hypersensitivity reactions to Antivenom, including one case of anaphylaxis. The median peak venom concentration in 37 systemically envenomed patients with serum available was 19 ng/mL (interquartile range, 12-50 ng/mL; range, 3-360 ng/mL), which did not correlate with clinical severity. In 17 patients who received Antivenom and had venom concentration measured, no venom was detected in serum after the first Antivenom dose, including nine who were given one vial of tiger Snake Antivenom. RBBS envenoming caused local effects, systemic symptoms, anticoagulant coagulopathy and, uncommonly, myotoxicity. One vial of tiger Snake or black Snake Antivenom appears to be sufficient to remove venom and neutralise reversible effects, but hypersensitivity reactions occurred in over a third of patients.
Kalana Maduwage - One of the best experts on this subject based on the ideXlab platform.
-
Pharmacodynamics and pharmacokinetics of Snake Antivenom
Sri Lanka Journal of Medicine, 2018Co-Authors: Bhagya Nikapitiya, Kalana MaduwageAbstract:Intact or fractionated immunoglobulins are used as Snake Antivenom to treat Snake envenomation. Intravenously administered Antivenom binds with Snake toxins in the circulation and neutralizes the toxins. Binding of Antivenom to venom in the central compartment prevents the distribution of venom to the peripheral tissues and enhances the elimination of venom. Reduction of Antivenom concentration in the central compartment is due to both distribution to the peripheral tissues and elimination. Pharmacokinetics of Snake Antivenom varies among the three different types of immunoglobulins, namely whole IgG, F(ab’)2 and Fab. Pharmacokinetics of F(ab’)2 Antivenom is best described by two compartment model with zero order input and linear elimination kinetics. Fab and F(ab’)2 Antivenom with smaller molecular masses have a larger volume of distribution than whole IgG Antivenom. A biphasic decline of intravenously administered whole IgG and F(ab’)2 Antivenom has been observed.
-
Population pharmacokinetics of an Indian F(ab')2 Snake Antivenom in patients with Russell's Viper (Daboia russelii) bites
PLoS neglected tropical diseases, 2015Co-Authors: Geoffrey K Isbister, Kalana Maduwage, Nicholas A Buckley, Ana Saiao, Shaluka Jayamanne, Shahmy Seyed, Fahim Mohamed, Umesh Chathuranga, Alexandre Mendes, Chandana AbeysingheAbstract:Background There is limited information on Antivenom pharmacokinetics. This study aimed to investigate the pharmacokinetics of an Indian Snake Antivenom in humans with Russell’s viper bites.
-
Snake Antivenom for Snake venom induced consumption coagulopathy
Cochrane Database of Systematic Reviews, 2015Co-Authors: Kalana Maduwage, Nicholas A Buckley, Janaka H De Silva, David G Lalloo, Geoffrey K IsbisterAbstract:Background Snake venom induced consumption coagulopathy is a major systemic effect of envenoming. Observational studies suggest that Antivenom improves outcomes for venom induced consumption coagulopathy in some Snakebites and not others. However, the effectiveness of Snake Antivenom in all cases of venom induced consumption coagulopathy is controversial. Objectives To assess the effect of Snake Antivenom as a treatment for venom induced consumption coagulopathy in people with Snake bite. Search methods The search was done on 30 January 2015. We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (OvidSP), three other sources, clinical trials registers, and we also screened reference lists. Selection criteria All completed, published or unpublished, randomised, controlled trials with a placebo or no treatment arm, where Snake Antivenom was administered for venom induced consumption coagulopathy in humans with Snake bites. Data collection and analysis Two authors reviewed the identified trials and independently applied the selection criteria. Main results No studies met the inclusion criteria for this review. Authors' conclusions Randomised placebo-controlled trials are required to investigate the effectiveness of Snake Antivenom for clinically relevant outcomes in patients with venom induced consumption coagulopathy resulting from Snake bite. Although ethically difficult, the routine administration of a treatment that has a significant risk of anaphylaxis cannot continue without strong evidence of benefit.
-
The Cochrane Library - Snake Antivenom for Snake venom induced consumption coagulopathy
The Cochrane database of systematic reviews, 2015Co-Authors: Kalana Maduwage, Nicholas A Buckley, David G Lalloo, H. Janaka De Silva, Geoffrey K IsbisterAbstract:Background Snake venom induced consumption coagulopathy is a major systemic effect of envenoming. Observational studies suggest that Antivenom improves outcomes for venom induced consumption coagulopathy in some Snakebites and not others. However, the effectiveness of Snake Antivenom in all cases of venom induced consumption coagulopathy is controversial. Objectives To assess the effect of Snake Antivenom as a treatment for venom induced consumption coagulopathy in people with Snake bite. Search methods The search was done on 30 January 2015. We searched the Cochrane Injuries Group's Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (OvidSP), three other sources, clinical trials registers, and we also screened reference lists. Selection criteria All completed, published or unpublished, randomised, controlled trials with a placebo or no treatment arm, where Snake Antivenom was administered for venom induced consumption coagulopathy in humans with Snake bites. Data collection and analysis Two authors reviewed the identified trials and independently applied the selection criteria. Main results No studies met the inclusion criteria for this review. Authors' conclusions Randomised placebo-controlled trials are required to investigate the effectiveness of Snake Antivenom for clinically relevant outcomes in patients with venom induced consumption coagulopathy resulting from Snake bite. Although ethically difficult, the routine administration of a treatment that has a significant risk of anaphylaxis cannot continue without strong evidence of benefit.
-
Use of immunoturbidimetry to detect venom-Antivenom binding using Snake venoms.
Journal of pharmacological and toxicological methods, 2013Co-Authors: Margaret A. O'leary, Kalana Maduwage, Geoffrey K IsbisterAbstract:Abstract Introduction Immunoturbidimetry studies the phenomenon of immunoprecipitation of antigens and antibodies in solution, where there is the formation of large, polymeric insoluble immunocomplexes that increase the turbidity of the solution. We used immunoturbidimetry to investigate the interaction between commercial Snake Antivenoms and Snake venoms, as well as cross-reactivity between different Snake venoms. Methods Serial dilutions of commercial Snake Antivenoms (100 μl) in water were placed in the wells of a microtitre plate and 100 μl of a venom solution (50 μg/ml in water) was added. Absorbance readings were taken at 340 nm every minute on a BioTek ELx808 plate reader at 37 °C. Limits imposed were a 30 minute cut-off and 0.004 as the lowest significant maximum increase. Reactions with rabbit antibodies were carried out similarly, except that antibody dilutions were in PBS. Results Mixing venom and Antivenom/antibodies resulted in an immediate increase in turbidity, which either reached a maximum or continued to increase until a 30 minute cut-off. There was a peak in absorbance readings for most Australian Snake venoms mixed with the corresponding commercial Antivenom, except for Pseudonaja textilis venom and brown Snake Antivenom. There was cross-reactivity between Naja naja venom from Sri Lanka and tiger Snake Antivenom indicated by turbidity when they were mixed. Mixing rabbit anti-Snake antibodies with Snake venoms resulted in increasing turbidity, but there was not a peak suggesting the antibodies were not sufficiently concentrated. The absorbance reading at pre-determined concentrations of rabbit antibodies mixed with different venoms was able to quantify the cross-reactivity between venoms. Indian Antivenoms from two manufacturers were tested against four Sri Lankan Snake venoms (Daboia russelli, N. naja, Echis carinatus and Bungarus caeruleus) and showed limited formation of immunocomplexes with Antivenom from one manufacturer. Discussion The turbidity test provides an easy and rapid way to compare and characterise interactions between Antivenoms and Snake venoms.
Bart J. Currie - One of the best experts on this subject based on the ideXlab platform.
-
current use of australian Snake Antivenoms and frequency of immediate type hypersensitivity reactions and anaphylaxis
The Medical Journal of Australia, 2008Co-Authors: Ellen Macdonald, Simon G A Brown, Julian White, Geoffrey K Isbister, Bart J. CurrieAbstract:Objective : To investigate current use of Australian Snake Antivenoms and the frequency and severity of immediate-type hypersensitivity reactions. Design: Nested prospective cohort study as part of the Australian Snakebite Project. Patients and setting:Patients receiving Snake Antivenom in Australian hospitals between 1 January 2002 and 30 November 2007. Main outcome measures: The use of CSL Limited Antivenom; frequency and severity of hypersensitivity reactions to Antivenom; premedication and treatment of these reactions. Results : Snake Antivenom was administered to 195 patients, mostly for venom-induced consumption coagulopathy (145 patients, 74%), followed by non-specific systemic effects (12%), neurotoxicity (5%) and myotoxicity (4%). Antivenom was given to nine patients (5%) without evidence of envenoming or who were bitten by a species of Snake for which Antivenom is not required. The commonest Antivenoms used were brown Snake (46%), tiger Snake (30%) and polyvalent (11%). The median dose was four vials (interquartile range, 2–5 vials), and 24 patients received two different types of Antivenom. Immediate-type hypersensitivity reactions occurred in 48 patients (25%); 21 satisfied our definition of anaphylaxis, with 11 moderate and 10 severe cases, including nine in which patients were hypotensive. The remaining 27 reactions were mild (skin only). Adrenaline was used in 26 cases with good effect. The frequency of reactions to tiger Snake (41%) and polyvalent (41%) Antivenoms was higher than that to brown Snake Antivenom (10%). Hypersensitivity reactions occurred in 11 of 40 patients receiving any form of premedication (28%) and in 2 of 11 given adrenaline for premedication (18%) versus 20 of 86 not receiving premedication (23%). Conclusions : Antivenom was used appropriately, and most commonly for coagulopathy. Hypersensitivity reactions were common, but most were not severe. The discretionary use of premedication was not associated with any reduction in reactions.
-
High rate of immediate systemic hypersensitivity reactions to tiger Snake Antivenom.
The Medical journal of Australia, 2006Co-Authors: Geoffrey K Isbister, Simon G A Brown, Julian White, Alan S Tankel, Mark Little, David Spain, Chris Gavaghan, Bart J. CurrieAbstract:[Extract] To The Editor: During a national multicentre study of Snake bites — the Australian Snakebite Project (ASP), involving over 40 hospitals — we have recently noted a high rate of early allergic reactions following the administration of tiger Snake Antivenom in Australia. People with suspected or definite Snake envenoming are recruited to ASP, and laboratory and clinical data and serial blood samples are collected to measure venom and Antivenom concentrations.