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Dr. Anjana Silva
1. Faculty of Medicine and Allied Sciences, Rajarata University of Sri Lanka, Saliyapura, 50008, Sri Lanka</br>2. Monash Venom Group, Monash University, Melbourne 3800, Australia

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0 Parasitology
0 Tropical Medicine
0 Toxinology
0 Snakebite antivenom public health
0 Snakebite

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Snakebite envenoming

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Journal article
Published: 26 April 2021 in Toxins
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Bites by many Asiatic and African cobras (Genus: Naja) cause severe local dermonecrosis and myonecrosis, resulting in permanent disabilities. We studied the time scale in which two Indian polyvalent antivenoms, VINS and Bharat, remain capable of preventing or reversing in vitro myotoxicity induced by common cobra (Naja naja) venom from Sri Lanka using the chick biventer cervicis nerve-muscle preparation. VINS fully prevented while Bharat partially prevented (both in manufacturer recommended concentrations) the myotoxicity induced by Naja naja venom (10 µg/mL) when added to the organ baths before the venom. However, both antivenoms were unable to reverse the myotoxicity when added to organ baths 5 and 20 min post-venom. In contrast, physical removal of the venom from the organ baths by washing the preparation 5 and 20 min after the venom resulted in full and partial prevention of the myotoxicity, respectively, indicating the lag period for irreversible cellular injury. This suggests that, although the antivenoms contain antibodies against cytotoxins of the Sri Lankan Naja naja venom, they are either unable to reach the target sites as efficiently as the cytotoxins, unable to bind efficiently with the toxins at the target sites, or the binding with the toxins simply fails to prevent the toxin-target interactions.

ACS Style

Umesha Madhushani; Prabhani Thakshila; Wayne Hodgson; Geoffrey Isbister; Anjana Silva. Effect of Indian Polyvalent Antivenom in the Prevention and Reversal of Local Myotoxicity Induced by Common Cobra (Naja naja) Venom from Sri Lanka In Vitro. Toxins 2021, 13, 308 .

AMA Style

Umesha Madhushani, Prabhani Thakshila, Wayne Hodgson, Geoffrey Isbister, Anjana Silva. Effect of Indian Polyvalent Antivenom in the Prevention and Reversal of Local Myotoxicity Induced by Common Cobra (Naja naja) Venom from Sri Lanka In Vitro. Toxins. 2021; 13 (5):308.

Chicago/Turabian Style

Umesha Madhushani; Prabhani Thakshila; Wayne Hodgson; Geoffrey Isbister; Anjana Silva. 2021. "Effect of Indian Polyvalent Antivenom in the Prevention and Reversal of Local Myotoxicity Induced by Common Cobra (Naja naja) Venom from Sri Lanka In Vitro." Toxins 13, no. 5: 308.

Journal article
Published: 01 December 2020 in Wilderness & Environmental Medicine
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Blood-bellied coral snake (Calliophis haematoetron) is a recently discovered forest-dwelling species of elapid hitherto known from 3 specimens found from central Sri Lanka. Herein we describe the first authenticated case of blood-bellied coral snakebite. The victim, an 11-mo-old infant who received the bite while handling the snake at her home, had mild transient swelling at the bite site. The patient had no clinical or laboratory evidence of systemic envenoming. We highlight the importance of clinicians being aware of the occurrence of this potentially medically important elapid snake in anthropogenic habitats.

ACS Style

Anjana Silva; Shyamalee Jayakody; Nishadi Ranasinghe; Asanka Manawaduge; Kavinda Perera. First Authenticated Case of a Bite by Rare and Elusive Blood-Bellied Coral Snake (Calliophis haematoetron). Wilderness & Environmental Medicine 2020, 31, 466 -469.

AMA Style

Anjana Silva, Shyamalee Jayakody, Nishadi Ranasinghe, Asanka Manawaduge, Kavinda Perera. First Authenticated Case of a Bite by Rare and Elusive Blood-Bellied Coral Snake (Calliophis haematoetron). Wilderness & Environmental Medicine. 2020; 31 (4):466-469.

Chicago/Turabian Style

Anjana Silva; Shyamalee Jayakody; Nishadi Ranasinghe; Asanka Manawaduge; Kavinda Perera. 2020. "First Authenticated Case of a Bite by Rare and Elusive Blood-Bellied Coral Snake (Calliophis haematoetron)." Wilderness & Environmental Medicine 31, no. 4: 466-469.

Research article
Published: 30 November 2020 in PLOS Neglected Tropical Diseases
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Delays in treatment seeking and antivenom administration remain problematic for snake envenoming. We aimed to describe the treatment seeking pattern and delays in admission to hospital and administration of antivenom in a cohort of authenticated snakebite patients. Adults (> 16 years), who presented with a confirmed snakebite from August 2013 to October 2014 were recruited from Anuradhapura Hospital. Demographic data, information on the circumstances of the bite, first aid, health-seeking behaviour, hospital admission, clinical features, outcomes and antivenom treatment were documented prospectively. There were 742 snakebite patients [median age: 40 years (IQR:27–51; males: 476 (64%)]. One hundred and five (14%) patients intentionally delayed treatment by a median of 45min (IQR:20-120min). Antivenom was administered a median of 230min (IQR:180–360min) post-bite, which didn’t differ between directly admitted and transferred patients; 21 (8%) receiving antivenom within 2h and 141 (55%) within 4h of the bite. However, transferred patients received antivenom sooner after admission to Anuradhapura hospital than those directly admitted (60min [IQR:30-120min] versus 120min [IQR:52-265min; p

ACS Style

Anjana Silva; Jiri Hlusicka; Nipuna Siribaddana; Subodha Waiddyanatha; Senaka Pilapitiya; Prasanna Weerawansa; Niroshan Lokunarangoda; Sujeewa Thalgaspitiya; Sisira Siribaddana; Geoffrey K. Isbister. Time delays in treatment of snakebite patients in rural Sri Lanka and the need for rapid diagnostic tests. PLOS Neglected Tropical Diseases 2020, 14, e0008914 .

AMA Style

Anjana Silva, Jiri Hlusicka, Nipuna Siribaddana, Subodha Waiddyanatha, Senaka Pilapitiya, Prasanna Weerawansa, Niroshan Lokunarangoda, Sujeewa Thalgaspitiya, Sisira Siribaddana, Geoffrey K. Isbister. Time delays in treatment of snakebite patients in rural Sri Lanka and the need for rapid diagnostic tests. PLOS Neglected Tropical Diseases. 2020; 14 (11):e0008914.

Chicago/Turabian Style

Anjana Silva; Jiri Hlusicka; Nipuna Siribaddana; Subodha Waiddyanatha; Senaka Pilapitiya; Prasanna Weerawansa; Niroshan Lokunarangoda; Sujeewa Thalgaspitiya; Sisira Siribaddana; Geoffrey K. Isbister. 2020. "Time delays in treatment of snakebite patients in rural Sri Lanka and the need for rapid diagnostic tests." PLOS Neglected Tropical Diseases 14, no. 11: e0008914.

Journal article
Published: 31 October 2020 in Toxins
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Coastal taipan (Oxyuranus scutellatus) envenoming causes life-threatening neuromuscular paralysis in humans. We studied the time period during which antivenom remains effective in preventing and arresting in vitro neuromuscular block caused by taipan venom and taipoxin. Venom showed predominant pre-synaptic neurotoxicity at 3 µg/mL and post-synaptic neurotoxicity at 10 µg/mL. Pre-synaptic neurotoxicity was prevented by addition of Australian polyvalent antivenom before the venom and taipoxin and, reversed when antivenom was added 5 min after venom and taipoxin. Antivenom only partially reversed the neurotoxicity when added 15 min after venom and had no significant effect when added 30 min after venom. In contrast, post-synaptic activity was fully reversed when antivenom was added 30 min after venom. The effect of antivenom on pre-synaptic neuromuscular block was reproduced by washing the bath at similar time intervals for 3 µg/mL, but not for 10 µg/mL. We found an approximate 10–15 min time window in which antivenom can prevent pre-synaptic neuromuscular block. This time window is likely to be longer in envenomed patients due to the delay in venom absorption. Similar effectiveness of antivenom and washing with 3 µg/mL venom suggests that antivenom most likely acts by neutralizing pre-synaptic toxins before they interfere with neurotransmission inside the motor nerve terminals.

ACS Style

Umesha Madhushani; Geoffrey K. Isbister; Theo Tasoulis; Wayne C. Hodgson; Anjana Silva. In-Vitro Neutralization of the Neurotoxicity of Coastal Taipan Venom by Australian Polyvalent Antivenom: The Window of Opportunity. Toxins 2020, 12, 690 .

AMA Style

Umesha Madhushani, Geoffrey K. Isbister, Theo Tasoulis, Wayne C. Hodgson, Anjana Silva. In-Vitro Neutralization of the Neurotoxicity of Coastal Taipan Venom by Australian Polyvalent Antivenom: The Window of Opportunity. Toxins. 2020; 12 (11):690.

Chicago/Turabian Style

Umesha Madhushani; Geoffrey K. Isbister; Theo Tasoulis; Wayne C. Hodgson; Anjana Silva. 2020. "In-Vitro Neutralization of the Neurotoxicity of Coastal Taipan Venom by Australian Polyvalent Antivenom: The Window of Opportunity." Toxins 12, no. 11: 690.

Review
Published: 10 September 2020 in Toxins
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Venom-induced consumption coagulopathy is the most important systemic effect of snake envenoming. Coagulation tests are helpful to accurately and promptly diagnose venom-induced consumption coagulopathy and administer antivenom, which is the only specific treatment available. However, bedside clotting tests play a major role in diagnosing coagulopathy in low-income settings, where the majority of snakebites occur. We conducted a literature search in MEDLINE® from 1946 to 30 November 2019, looking for research articles describing clinical studies on bedside coagulation tests in snakebite patients. Out of 442 articles identified, 147 articles describing bedside clotting assays were included in the review. Three main bedside clotting tests were identified, namely the Lee–White clotting test, 20-min whole blood clotting time and venous clotting time. Although the original Lee–White clotting test has never been validated for snake envenoming, a recently validated version has been used in some South American countries. The 20-min whole blood clotting time test is the most commonly used test in a wide range of settings and for taxonomically diverse snake species. Venous clotting time is almost exclusively used in Thailand. Many validation studies have methodological limitations, including small sample size, lack of case-authentication, the inclusion of a heterogeneous mix of snakebites and inappropriate uses of gold standard tests. The observation times for bedside clotting tests were arbitrary, without proper scientific justification. Future research needs to focus on improving the existing 20-min whole blood clotting test, and also on looking for alternative bedside coagulation tests which are cheap, reliable and quicker.

ACS Style

Supun Wedasingha; Geoffrey Isbister; Anjana Silva. Bedside Coagulation Tests in Diagnosing Venom-Induced Consumption Coagulopathy in Snakebite. Toxins 2020, 12, 583 .

AMA Style

Supun Wedasingha, Geoffrey Isbister, Anjana Silva. Bedside Coagulation Tests in Diagnosing Venom-Induced Consumption Coagulopathy in Snakebite. Toxins. 2020; 12 (9):583.

Chicago/Turabian Style

Supun Wedasingha; Geoffrey Isbister; Anjana Silva. 2020. "Bedside Coagulation Tests in Diagnosing Venom-Induced Consumption Coagulopathy in Snakebite." Toxins 12, no. 9: 583.

Journal article
Published: 03 September 2020 in Toxicon
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Reporting of snakebite is poor in areas where they are most common. Comparatively, bites by snakes of high medical importance are likely to be documented than snakes of lesser medical importance. This study aims to describe the demographic, epidemiological and, clinical data of patients who were presented during a 49-month study period to a tertiary care center in rural Sri Lanka following authenticated bites by snakes of lesser medical importance. Of the total of 2362 confirmed snakebite patients during the study period, 517 (22%) presented with the offending snake specimen. Of them, 76 (15%) were identified as snakes of lesser medical importance and were included in this study. There were 41 (54%) females. The median ages of females and males were 35 and 43 years respectively. Most patients (86%) were bitten indoors or at home gardens. More than half of them were bitten between 1800 and 0000 h. Most bites (54%) had occurred to the ankle or below. The patients were bitten by 12 species of colubrids, one pythonid (Python molurus), and one viperid (Trimeresurus trigonocephalus). The snake species that caused the most-number of bites was the Trinket snake (Coelognathus helena) (n = 15). Three species of wolf-snakes, Lycodon aulicus, L. anamallensis, and L. striatus were responsible for 12, 11, and 5 bites respectively. Most of the patients (55%) presented to the local hospital and subsequently transferred to the study hospital for further management. None of the patients developed systemic envenoming and five developed mild local pain and swelling. Fifty-six (74%) patients were discharged on the following day, while 18 (24%) were discharged on the third day. There is a need to educate medical personnel working the peripheral hospital on how to identify medically lesser important snakes to avoid unnecessary transfers.

ACS Style

Sujeewa Thalgaspitiya; Geoffrey Isbister; Kanishka Ukuwela; Chamara Sarathchandra; Hemal Senanayake; Niroshan Lokunarangoda; Sisira Siribaddana; Anjana Silva. Bites by snakes of lesser medical importance in a cohort of snakebite patients from rural Sri Lanka. Toxicon 2020, 187, 105 -110.

AMA Style

Sujeewa Thalgaspitiya, Geoffrey Isbister, Kanishka Ukuwela, Chamara Sarathchandra, Hemal Senanayake, Niroshan Lokunarangoda, Sisira Siribaddana, Anjana Silva. Bites by snakes of lesser medical importance in a cohort of snakebite patients from rural Sri Lanka. Toxicon. 2020; 187 ():105-110.

Chicago/Turabian Style

Sujeewa Thalgaspitiya; Geoffrey Isbister; Kanishka Ukuwela; Chamara Sarathchandra; Hemal Senanayake; Niroshan Lokunarangoda; Sisira Siribaddana; Anjana Silva. 2020. "Bites by snakes of lesser medical importance in a cohort of snakebite patients from rural Sri Lanka." Toxicon 187, no. : 105-110.

Journal article
Published: 30 July 2020 in Toxins
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Intra-specific venom variation has the potential to provide important insights into the evolution of snake venom, but remains a relatively neglected aspect of snake venom studies. We investigated the venom from 13 individual coastal taipans Oxyuranus scutellatus from four localities on the north-east coast of Australia, spanning a distance of 2000km. The intra-specific variation in taipan venom was considerably less than the inter-specific variation between it and the other Australian elapids to which it was compared. The electrophoretic venom profile of O. scutellatus was visually different to six other genera of Australian elapids, but not to its congener inland taipan O. microlepidotus. There was minimal geographical variation in taipan venom, as the intra-population variation exceeded the inter-population variation for enzymatic activity, procoagulant activity, and the abundance of neurotoxins. The pre-synaptic neurotoxin (taipoxin) was more abundant than the post-synaptic neurotoxins (3FTx), with a median of 11.0% (interquartile range (IQR): 9.7% to 18.3%; range: 6.7% to 23.6%) vs. a median of 3.4% (IQR: 0.4% to 6.7%; range: 0% to 8.1%). Three taipan individuals almost completely lacked post-synaptic neurotoxins, which was not associated with geography and occurred within two populations. We found no evidence of sexual dimorphism in taipan venom. Our study provides a basis for evaluating the significance of intra-specific venom variation within a phylogenetic context by comparing it to the inter-specific and inter-generic variation. The considerable intra-population variation we observed supports the use of several unpooled individuals from each population when making inter-specific comparisons.

ACS Style

Theo Tasoulis; Anjana Silva; Punnam Chander Veerati; Mark Baker; Wayne C. Hodgson; Nathan Dunstan; Geoffrey K. Isbister. Intra-Specific Venom Variation in the Australian Coastal Taipan Oxyuranus scutellatus. Toxins 2020, 12, 485 .

AMA Style

Theo Tasoulis, Anjana Silva, Punnam Chander Veerati, Mark Baker, Wayne C. Hodgson, Nathan Dunstan, Geoffrey K. Isbister. Intra-Specific Venom Variation in the Australian Coastal Taipan Oxyuranus scutellatus. Toxins. 2020; 12 (8):485.

Chicago/Turabian Style

Theo Tasoulis; Anjana Silva; Punnam Chander Veerati; Mark Baker; Wayne C. Hodgson; Nathan Dunstan; Geoffrey K. Isbister. 2020. "Intra-Specific Venom Variation in the Australian Coastal Taipan Oxyuranus scutellatus." Toxins 12, no. 8: 485.

Review article
Published: 20 March 2020 in Biochemical Society Transactions
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Snakebite is a major public health issue in the rural tropics. Antivenom is the only specific treatment currently available. We review the history, mechanism of action and current developments in snake antivenoms. In the late nineteenth century, snake antivenoms were first developed by raising hyperimmune serum in animals, such as horses, against snake venoms. Hyperimmune serum was then purified to produce whole immunoglobulin G (IgG) antivenoms. IgG was then fractionated to produce F(ab) and F(ab′)2 antivenoms to reduce adverse reactions and increase efficacy. Current commercial antivenoms are polyclonal mixtures of antibodies or their fractions raised against all toxin antigens in a venom(s), irrespective of clinical importance. Over the last few decades there have been small incremental improvements in antivenoms, to make them safer and more effective. A number of recent developments in biotechnology and toxinology have contributed to this. Proteomics and transcriptomics have been applied to venom toxin composition (venomics), improving our understanding of medically important toxins. In addition, it has become possible to identify toxins that contain epitopes recognized by antivenom molecules (antivenomics). Integration of the toxinological profile of a venom and its composition to identify medically relevant toxins improved this. Furthermore, camelid, humanized and fully human monoclonal antibodies and their fractions, as well as enzyme inhibitors have been experimentally developed against venom toxins. Translation of such technology into commercial antivenoms requires overcoming the high costs, limited knowledge of venom and antivenom pharmacology, and lack of reliable animal models. Addressing such should be the focus of antivenom research.

ACS Style

Anjana Silva; Geoffrey K. Isbister. Current research into snake antivenoms, their mechanisms of action and applications. Biochemical Society Transactions 2020, 48, 537 -546.

AMA Style

Anjana Silva, Geoffrey K. Isbister. Current research into snake antivenoms, their mechanisms of action and applications. Biochemical Society Transactions. 2020; 48 (2):537-546.

Chicago/Turabian Style

Anjana Silva; Geoffrey K. Isbister. 2020. "Current research into snake antivenoms, their mechanisms of action and applications." Biochemical Society Transactions 48, no. 2: 537-546.

Journal article
Published: 27 December 2019 in Scientific Reports
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We investigated the cardiovascular effects of venoms from seven medically important species of snakes: Australian Eastern Brown snake (Pseudonaja textilis), Sri Lankan Russell’s viper (Daboia russelii), Javanese Russell’s viper (D. siamensis), Gaboon viper (Bitis gabonica), Uracoan rattlesnake (Crotalus vegrandis), Carpet viper (Echis ocellatus) and Puff adder (Bitis arietans), and identified two distinct patterns of effects: i.e. rapid cardiovascular collapse and prolonged hypotension.P. textilis(5 µg/kg, i.v.) andE. ocellatus(50 µg/kg, i.v.) venoms induced rapid (i.e. within 2 min) cardiovascular collapse in anaesthetised rats.P. textilis(20 mg/kg, i.m.) caused collapse within 10 min.D. russelii(100 µg/kg, i.v.) andD. siamensis(100 µg/kg, i.v.) venoms caused ‘prolonged hypotension’, characterised by a persistent decrease in blood pressure with recovery.D. russeliivenom (50 mg/kg and 100 mg/kg, i.m.) also caused prolonged hypotension. A priming dose ofP. textilisvenom (2 µg/kg, i.v.) prevented collapse byE. ocellatusvenom (50 µg/kg, i.v.), but had no significant effect on subsequent additionof D. russeliivenom (1 mg/kg, i.v). Two priming doses (1 µg/kg, i.v.) ofE. ocellatusvenom prevented collapse byE. ocellatusvenom (50 µg/kg, i.v.).B. gabonica,C. vegrandisandB. arietans(all at 200 µg/kg, i.v.) induced mild transient hypotension. Artificial respiration preventedD. russeliivenom induced prolonged hypotension but not rapid cardiovascular collapse fromE. ocellatusvenom.D. russeliivenom (0.001–1 μg/ml) caused concentration-dependent relaxation (EC50 = 82.2 ± 15.3 ng/ml, Rmax = 91 ± 1%) in pre-contracted mesenteric arteries. In contrast,E. ocellatusvenom (1 µg/ml) only produced a maximum relaxant effect of 27 ± 14%, suggesting that rapid cardiovascular collapse is unlikely to be due to peripheral vasodilation. The prevention of rapid cardiovascular collapse, by ‘priming’ doses of venom, supports a role for depletable endogenous mediators in this phenomenon.

ACS Style

Rahini Kakumanu; Barbara K. Kemp-Harper; Anjana Silva; Sanjaya Kuruppu; Geoffrey K. Isbister; Wayne C. Hodgson. An in vivo examination of the differences between rapid cardiovascular collapse and prolonged hypotension induced by snake venom. Scientific Reports 2019, 9, 1 -9.

AMA Style

Rahini Kakumanu, Barbara K. Kemp-Harper, Anjana Silva, Sanjaya Kuruppu, Geoffrey K. Isbister, Wayne C. Hodgson. An in vivo examination of the differences between rapid cardiovascular collapse and prolonged hypotension induced by snake venom. Scientific Reports. 2019; 9 (1):1-9.

Chicago/Turabian Style

Rahini Kakumanu; Barbara K. Kemp-Harper; Anjana Silva; Sanjaya Kuruppu; Geoffrey K. Isbister; Wayne C. Hodgson. 2019. "An in vivo examination of the differences between rapid cardiovascular collapse and prolonged hypotension induced by snake venom." Scientific Reports 9, no. 1: 1-9.

Review
Published: 31 March 2019 in Toxins
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Long-term effects of envenoming compromise the quality of life of the survivors of snakebite. We searched MEDLINE (from 1946) and EMBASE (from 1947) until October 2018 for clinical literature on the long-term effects of snake envenoming using different combinations of search terms. We classified conditions that last or appear more than six weeks following envenoming as long term or delayed effects of envenoming. Of 257 records identified, 51 articles describe the long-term effects of snake envenoming and were reviewed. Disability due to amputations, deformities, contracture formation, and chronic ulceration, rarely with malignant change, have resulted from local necrosis due to bites mainly from African and Asian cobras, and Central and South American Pit-vipers. Progression of acute kidney injury into chronic renal failure in Russell’s viper bites has been reported in several studies from India and Sri Lanka. Neuromuscular toxicity does not appear to result in long-term effects. Endocrine anomalies such as delayed manifestation of hypopituitarism following Russell’s viper bites have been reported. Delayed psychological effects such as depressive symptoms, post-traumatic stress disorder and somatisation have been reported. Blindness due to primary and secondary effects of venom is a serious, debilitating effect. In general, the available studies have linked a clinical effect to a snakebite in retrospect, hence lacked accurate snake authentication, details of acute management and baseline data and are unable to provide a detailed picture of clinical epidemiology of the long-term effects of envenoming. In the future, it will be important to follow cohorts of snakebite patients for a longer period of time to understand the true prevalence, severity, clinical progression and risk factors of long-term effects of snake envenoming.

ACS Style

Subodha Waiddyanatha; Anjana Silva; Sisira Siribaddana; Geoffrey K. Isbister. Long-term Effects of Snake Envenoming. Toxins 2019, 11, 193 .

AMA Style

Subodha Waiddyanatha, Anjana Silva, Sisira Siribaddana, Geoffrey K. Isbister. Long-term Effects of Snake Envenoming. Toxins. 2019; 11 (4):193.

Chicago/Turabian Style

Subodha Waiddyanatha; Anjana Silva; Sisira Siribaddana; Geoffrey K. Isbister. 2019. "Long-term Effects of Snake Envenoming." Toxins 11, no. 4: 193.

Case report
Published: 15 March 2019 in Toxicon
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The Merrem's hump-nosed viper (H. hypnale) causes many snakebites in South India and Sri Lanka. At present no antivenom is available for envenomings by this snake. A 42-year-old male bitten by a large H. hypnale, presented within 30 min of the bite and had a cardiac arrest soon after admission. This responded to standard advanced life support, but he had an unrecordably high international normalised ratio (INR), activated partial thromboplastin time and unrecordably low fibrinogen, consistent with a complete venom-induced consumption coagulopathy. In the absence of antivenom, a total of 1680ml of fresh frozen plasma (FFP) was transfused 5.5 and 16 h post-bite. The coagulopathy did not improve with the administration of FFP and a further elevation of D-Dimer after FFP suggested consumption of transfused clotting factors. The coagulopathy resolved after 72 h. The patient did not develop any bleeding complications, acute kidney injury or evidence of thrombotic microangiopathy and was discharged 8 days after the bite. This case suggests that early FFP for VICC in H. hypnale envenoming may worsen the coagulopathy in the absence of antivenom and cannot be recommended.

ACS Style

Harendra Kumara; Nimal Seneviratne; Dilini S. Jayaratne; Sisira Siribaddana; Geoffrey K. Isbister; Anjana Silva. Severe coagulopathy in Merrem's hump-nosed pit viper (Hypnale hypnale) envenoming unresponsive to fresh frozen plasma: A case report. Toxicon 2019, 163, 19 -22.

AMA Style

Harendra Kumara, Nimal Seneviratne, Dilini S. Jayaratne, Sisira Siribaddana, Geoffrey K. Isbister, Anjana Silva. Severe coagulopathy in Merrem's hump-nosed pit viper (Hypnale hypnale) envenoming unresponsive to fresh frozen plasma: A case report. Toxicon. 2019; 163 ():19-22.

Chicago/Turabian Style

Harendra Kumara; Nimal Seneviratne; Dilini S. Jayaratne; Sisira Siribaddana; Geoffrey K. Isbister; Anjana Silva. 2019. "Severe coagulopathy in Merrem's hump-nosed pit viper (Hypnale hypnale) envenoming unresponsive to fresh frozen plasma: A case report." Toxicon 163, no. : 19-22.

Journal article
Published: 01 January 2019 in Toxicology Communications
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ACS Style

Anjana Silva; E. Michael Sedgwick; Prasanna Weerawansa; Senaka Pilapitiya; Vajira Weerasinghe; Nicholas Buckley; Sisira Siribaddana; Geoffrey K. Isbister. Sub-clinical neuromuscular dysfunction after envenoming by Merrem’s hump-nosed pit viper (Hypnale hypnale). Toxicology Communications 2019, 3, 23 -28.

AMA Style

Anjana Silva, E. Michael Sedgwick, Prasanna Weerawansa, Senaka Pilapitiya, Vajira Weerasinghe, Nicholas Buckley, Sisira Siribaddana, Geoffrey K. Isbister. Sub-clinical neuromuscular dysfunction after envenoming by Merrem’s hump-nosed pit viper (Hypnale hypnale). Toxicology Communications. 2019; 3 (1):23-28.

Chicago/Turabian Style

Anjana Silva; E. Michael Sedgwick; Prasanna Weerawansa; Senaka Pilapitiya; Vajira Weerasinghe; Nicholas Buckley; Sisira Siribaddana; Geoffrey K. Isbister. 2019. "Sub-clinical neuromuscular dysfunction after envenoming by Merrem’s hump-nosed pit viper (Hypnale hypnale)." Toxicology Communications 3, no. 1: 23-28.

Case report
Published: 02 August 2018 in Journal of Medical Case Reports
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Hump-nosed pit vipers (Genus: Hypnale) are medically important snakes in Sri Lanka and South India. Merrem’s Hump-nosed pit viper (Hypnale hypnale) frequently leads to potentially fatal envenomings in Sri Lanka and India. Venom-induced consumption coagulopathay (VICC), local envenoming and acute kidney injury (AKI) are the commonest effects of the envenoming by this snake. We report a previously unreported presentation of H. hypnale envenoming, with an isolated urinary salt loss leading to moderate hyponatraemia resulting seizures. The patient was treated with careful fluid and electrolyte management. No antivenom is currently available for H. hypnale envenoming. In the absence of any evidence of venom induced consumptive coagulopathy, acute kidney injury and cerebral haemorrhage, we hypothesize that this effect is likely due to the presence of a natriuretic peptide in H. hypnale venom, similar to the natriuretic peptides identified in few other snake venoms.

ACS Style

Umesh De Silva; Chamara Sarathchandra; Hemal Senanayake; Senaka Pilapitiya; Sisira Siribaddana; Anjana Silva. Hyponatraemia and seizures in Merrem’s hump-nosed pit viper (Hypnale hypnale) envenoming: a case report. Journal of Medical Case Reports 2018, 12, 1 -3.

AMA Style

Umesh De Silva, Chamara Sarathchandra, Hemal Senanayake, Senaka Pilapitiya, Sisira Siribaddana, Anjana Silva. Hyponatraemia and seizures in Merrem’s hump-nosed pit viper (Hypnale hypnale) envenoming: a case report. Journal of Medical Case Reports. 2018; 12 (1):1-3.

Chicago/Turabian Style

Umesh De Silva; Chamara Sarathchandra; Hemal Senanayake; Senaka Pilapitiya; Sisira Siribaddana; Anjana Silva. 2018. "Hyponatraemia and seizures in Merrem’s hump-nosed pit viper (Hypnale hypnale) envenoming: a case report." Journal of Medical Case Reports 12, no. 1: 1-3.

Original article
Published: 01 August 2018 in Cellular and Molecular Life Sciences
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Snake venom α-neurotoxins potently inhibit rodent nicotinic acetylcholine receptors (nAChRs), but their activity on human receptors and their role in human paralysis from snakebite remain unclear. We demonstrate that two short-chain α-neurotoxins (SαNTx) functionally inhibit human muscle-type nAChR, but are markedly more reversible than against rat receptors. In contrast, two long-chain α-neurotoxins (LαNTx) show no species differences in potency or reversibility. Mutant studies identified two key residues accounting for this. Proteomic and clinical data suggest that paralysis in human snakebites is not associated with SαNTx, but with LαNTx, such as in cobras. Neuromuscular blockade produced by both subclasses of α-neurotoxins was reversed by antivenom in rat nerve–muscle preparations, supporting its effectiveness in human post-synaptic paralysis.

ACS Style

Anjana Silva; Ben Cristofori-Armstrong; Lachlan D. Rash; Wayne C. Hodgson; Geoffrey K. Isbister. Defining the role of post-synaptic α-neurotoxins in paralysis due to snake envenoming in humans. Cellular and Molecular Life Sciences 2018, 75, 4465 -4478.

AMA Style

Anjana Silva, Ben Cristofori-Armstrong, Lachlan D. Rash, Wayne C. Hodgson, Geoffrey K. Isbister. Defining the role of post-synaptic α-neurotoxins in paralysis due to snake envenoming in humans. Cellular and Molecular Life Sciences. 2018; 75 (23):4465-4478.

Chicago/Turabian Style

Anjana Silva; Ben Cristofori-Armstrong; Lachlan D. Rash; Wayne C. Hodgson; Geoffrey K. Isbister. 2018. "Defining the role of post-synaptic α-neurotoxins in paralysis due to snake envenoming in humans." Cellular and Molecular Life Sciences 75, no. 23: 4465-4478.

Comment
Published: 12 July 2018 in The Lancet
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Joshua Longbottom and colleagues1x1Longbottom, J, Shearer, FM, Devine, M et al. Vulnerability to snakebite envenoming: a global mapping of hotspots. Lancet. 2018; (published online July 12.)http://dx.doi.org/S0140-6736(18)31224-8.PubMed | Google ScholarSee all References highlight once again that snake envenoming is a major health issue affecting remote and rural regions of the tropics. They use information about venomous snake distribution, health-care access, and availability of antivenom to identify the most vulnerable populations to snakebite. This modelling study1x1Longbottom, J, Shearer, FM, Devine, M et al. Vulnerability to snakebite envenoming: a global mapping of hotspots. Lancet. 2018; (published online July 12.)http://dx.doi.org/S0140-6736(18)31224-8.PubMed | Google ScholarSee all References reported in The Lancet identified about 92·66 million people living in regions vulnerable to snakebite, including sub-Saharan Africa, southeast Asia, and Indonesia. The major limitation of Longbottom and colleagues' study1x1Longbottom, J, Shearer, FM, Devine, M et al. Vulnerability to snakebite envenoming: a global mapping of hotspots. Lancet. 2018; (published online July 12.)http://dx.doi.org/S0140-6736(18)31224-8.PubMed | Google ScholarSee all References is that they do not report actual snakebites—making a number of assumptions, such as different venomous snakes and different human populations living together. This assumption results in the same risk of snake envenoming across different geographical regions, which is unlikely to be true. They also used a Nigerian retrospective observational study,2x2Habib, AG and Abubakar, SB. Factors affecting snakebite mortality in north-eastern Nigeria. Int Health. 2011; 3: 50–55Summary | Full Text | Full Text PDF | PubMed | Scopus (17) | Google ScholarSee all References with more than 90% of bites from Echis ocellatus (saw-scaled viper), in which deaths are due to coagulopathy and bleeding, to estimate the effect of delay to antivenom on mortality. The effectiveness of antivenom is highly species specific and different for neurotoxic envenoming,3x3Silva, A, Maduwage, K, Sedgwick, M et al. Neuromuscular effects of common krait (Bungarus caeruleus) envenoming in Sri Lanka. PLoS Negl Trop Dis. 2016; 10: e0004368Crossref | PubMed | Scopus (13) | Google ScholarSee all References and cannot be administered early enough to prevent early prehospital deaths from cardiac arrest.4x4Johnston, CI, Ryan, NM, Page, CB et al. The Australian snakebite project, 2005–2015 (ASP-20). Med J Aust. 2017; 207: 119–125Crossref | PubMed | Scopus (2) | Google ScholarSee all References Reassuringly, Longbottom and colleagues identified the same geographical regions as did a previously published global study of snakebites, which reported between 421 000 and 1 841 000 additional envenomings occurring annually, and 20 000–94 000 deaths.5x5Kasturiratne, A, Wickremasinghe, AR, de Silva, N et al. The global burden of snakebite: a literature analysis and modelling based on regional estimates of envenoming and deaths. PLoS Med. 2008; 5: e218Crossref | PubMed | Scopus (593) | Google ScholarSee all References

ACS Style

Geoffrey K Isbister; Anjana Silva. Addressing the global challenge of snake envenoming. The Lancet 2018, 392, 619 -620.

AMA Style

Geoffrey K Isbister, Anjana Silva. Addressing the global challenge of snake envenoming. The Lancet. 2018; 392 (10148):619-620.

Chicago/Turabian Style

Geoffrey K Isbister; Anjana Silva. 2018. "Addressing the global challenge of snake envenoming." The Lancet 392, no. 10148: 619-620.

Review
Published: 19 April 2017 in Toxins
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Antivenom therapy is currently the standard practice for treating neuromuscular dysfunction in snake envenoming. We reviewed the clinical and experimental evidence-base for the efficacy and effectiveness of antivenom in snakebite neurotoxicity. The main site of snake neurotoxins is the neuromuscular junction, and the majority are either: (1) pre-synaptic neurotoxins irreversibly damaging the presynaptic terminal; or (2) post-synaptic neurotoxins that bind to the nicotinic acetylcholine receptor. Pre-clinical tests of antivenom efficacy for neurotoxicity include rodent lethality tests, which are problematic, and in vitro pharmacological tests such as nerve-muscle preparation studies, that appear to provide more clinically meaningful information. We searched MEDLINE (from 1946) and EMBASE (from 1947) until March 2017 for clinical studies. The search yielded no randomised placebo-controlled trials of antivenom for neuromuscular dysfunction. There were several randomised and non-randomised comparative trials that compared two or more doses of the same or different antivenom, and numerous cohort studies and case reports. The majority of studies available had deficiencies including poor case definition, poor study design, small sample size or no objective measures of paralysis. A number of studies demonstrated the efficacy of antivenom in human envenoming by clearing circulating venom. Studies of snakes with primarily pre-synaptic neurotoxins, such as kraits (Bungarus spp.) and taipans (Oxyuranus spp.) suggest that antivenom does not reverse established neurotoxicity, but early administration may be associated with decreased severity or prevent neurotoxicity. Small studies of snakes with mainly post-synaptic neurotoxins, including some cobra species (Naja spp.), provide preliminary evidence that neurotoxicity may be reversed with antivenom, but placebo controlled studies with objective outcome measures are required to confirm this.

ACS Style

Ana Maria Moura Da Silva; Wayne C. Hodgson; Geoffrey K. Isbister. Antivenom for Neuromuscular Paralysis Resulting From Snake Envenoming. Toxins 2017, 9, 143 .

AMA Style

Ana Maria Moura Da Silva, Wayne C. Hodgson, Geoffrey K. Isbister. Antivenom for Neuromuscular Paralysis Resulting From Snake Envenoming. Toxins. 2017; 9 (4):143.

Chicago/Turabian Style

Ana Maria Moura Da Silva; Wayne C. Hodgson; Geoffrey K. Isbister. 2017. "Antivenom for Neuromuscular Paralysis Resulting From Snake Envenoming." Toxins 9, no. 4: 143.

Article
Published: 21 March 2017 in Cochrane Database of Systematic Reviews
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This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:

ACS Style

Anjana Silva; Kalana Maduwage; Nick A Buckley; David G Lalloo; H Janaka De Silva; Geoffrey K Isbister. Antivenom for snake venom-induced neuromuscular paralysis. Cochrane Database of Systematic Reviews 2017, 2017, 1 .

AMA Style

Anjana Silva, Kalana Maduwage, Nick A Buckley, David G Lalloo, H Janaka De Silva, Geoffrey K Isbister. Antivenom for snake venom-induced neuromuscular paralysis. Cochrane Database of Systematic Reviews. 2017; 2017 (3):1.

Chicago/Turabian Style

Anjana Silva; Kalana Maduwage; Nick A Buckley; David G Lalloo; H Janaka De Silva; Geoffrey K Isbister. 2017. "Antivenom for snake venom-induced neuromuscular paralysis." Cochrane Database of Systematic Reviews 2017, no. 3: 1.

Research article
Published: 02 December 2016 in PLOS Neglected Tropical Diseases
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Sri Lankan Russell’s viper (Daboia russelii) envenoming is reported to cause myotoxicity and neurotoxicity, which are different to the effects of envenoming by most other populations of Russell’s vipers. This study aimed to investigate evidence of myotoxicity in Russell’s viper envenoming, response to antivenom and the toxins responsible for myotoxicity. Clinical features of myotoxicity were assessed in authenticated Russell’s viper bite patients admitted to a Sri Lankan teaching hospital. Toxins were isolated using high-performance liquid chromatography. In-vitro myotoxicity of the venom and toxins was investigated in chick biventer nerve-muscle preparations. Of 245 enrolled patients, 177 (72.2%) had local myalgia and 173 (70.6%) had local muscle tenderness. Generalized myalgia and muscle tenderness were present in 35 (14.2%) and 29 (11.8%) patients, respectively. Thirty-seven patients had high (>300 U/l) serum creatine kinase (CK) concentrations in samples 24h post-bite (median: 666 U/l; maximum: 1066 U/l). Peak venom and 24h CK concentrations were not associated (Spearman’s correlation; p = 0.48). The 24h CK concentrations differed in patients without myotoxicity (median 58 U/l), compared to those with local (137 U/l) and generalised signs/symptoms of myotoxicity (107 U/l; p = 0.049). Venom caused concentration-dependent inhibition of direct twitches in the chick biventer cervicis nerve-muscle preparation, without completely abolishing direct twitches after 3 h even at 80 μg/ml. Indian polyvalent antivenom did not prevent in-vitro myotoxicity at recommended concentrations. Two phospholipase A2 toxins with molecular weights of 13kDa, U1-viperitoxin-Dr1a (19.2% of venom) and U1-viperitoxin-Dr1b (22.7% of venom), concentration dependently inhibited direct twitches in the chick biventer cervicis nerve-muscle preparation. At 3 μM, U1-viperitoxin-Dr1a abolished twitches, while U1-viperitoxin-Dr1b caused 70% inhibition of twitch force after 3h. Removal of both toxins from whole venom resulted in no in-vitro myotoxicity. The study shows that myotoxicity in Sri Lankan Russell’s viper envenoming is mild and non-life threatening, and due to two PLA2 toxins with weak myotoxic properties. There are many gaps in our knowledge of muscle damage caused by snake venoms. Russell’s vipers are more medically important than any other snake in Asia. Sri Lankan Russell’s viper (Daboia russelii) bites have been reported to cause muscle damage in humans, which is not reported for other Russell’s vipers. The aim of the present study was to investigate the onset, severity and resolution of the muscle damage and to identify the toxins responsible for myotoxicity. For this, we studied muscle damage in 245 patients with confirmed Sri Lankan Russell’s viper bites. Patients reported local muscle pain in 72% of cases and generalised muscle pain in 15%. None had severe muscle damage and the symptoms resolved in 80% of patients within 4 days. Measurement of biomarkers of muscle damage in patient blood was consistent with only mild muscle injury, even in patients with symptoms. Two toxins were isolated from Sri Lankan Russell’s viper venom that had similar myotoxic activity to whole venom in chick muscle preparations. Both toxins were weak myotoxins, consistent with what was seen in patients.

ACS Style

Anjana Silva; Christopher Johnston; Sanjaya Kuruppu; Daniela Kneisz; Kalana Maduwage; Oded Kleifeld; A. Ian Smith; Sisira Siribaddana; Nicholas Buckley; Wayne Hodgson; Geoffrey K. Isbister. Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell’s Viper (Daboia russelii) Envenoming. PLOS Neglected Tropical Diseases 2016, 10, e0005172 .

AMA Style

Anjana Silva, Christopher Johnston, Sanjaya Kuruppu, Daniela Kneisz, Kalana Maduwage, Oded Kleifeld, A. Ian Smith, Sisira Siribaddana, Nicholas Buckley, Wayne Hodgson, Geoffrey K. Isbister. Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell’s Viper (Daboia russelii) Envenoming. PLOS Neglected Tropical Diseases. 2016; 10 (12):e0005172.

Chicago/Turabian Style

Anjana Silva; Christopher Johnston; Sanjaya Kuruppu; Daniela Kneisz; Kalana Maduwage; Oded Kleifeld; A. Ian Smith; Sisira Siribaddana; Nicholas Buckley; Wayne Hodgson; Geoffrey K. Isbister. 2016. "Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell’s Viper (Daboia russelii) Envenoming." PLOS Neglected Tropical Diseases 10, no. 12: e0005172.

Journal article
Published: 18 October 2016 in Toxins
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There is limited information on the cross-neutralisation of neurotoxic venoms with antivenoms. Cross-neutralisation of the in vitro neurotoxicity of four Asian and four Australian snake venoms, four post-synaptic neurotoxins (α-bungarotoxin, α-elapitoxin-Nk2a, α-elapitoxin-Ppr1 and α-scutoxin; 100 nM) and one pre-synaptic neurotoxin (taipoxin; 100 nM) was studied with five antivenoms: Thai cobra antivenom (TCAV), death adder antivenom (DAAV), Thai neuro polyvalent antivenom (TNPAV), Indian Polyvalent antivenom (IPAV) and Australian polyvalent antivenom (APAV). The chick biventer cervicis nerve-muscle preparation was used for this study. Antivenom was added to the organ bath 20 min prior to venom. Pre- and post-synaptic neurotoxicity of Bungarus caeruleus and Bungarus fasciatus venoms was neutralised by all antivenoms except TCAV, which did not neutralise pre-synaptic activity. Post-synaptic neurotoxicity of Ophiophagus hannah was neutralised by all antivenoms, and Naja kaouthia by all antivenoms except IPAV. Pre- and post-synaptic neurotoxicity of Notechis scutatus was neutralised by all antivenoms, except TCAV, which only partially neutralised pre-synaptic activity. Pre- and post-synaptic neurotoxicity of Oxyuranus scutellatus was neutralised by TNPAV and APAV, but TCAV and IPAV only neutralised post-synaptic neurotoxicity. Post-synaptic neurotoxicity of Acanthophis antarcticus was neutralised by all antivenoms except IPAV. Pseudonaja textillis post-synaptic neurotoxicity was only neutralised by APAV. The α-neurotoxins were neutralised by TNPAV and APAV, and taipoxin by all antivenoms except IPAV. Antivenoms raised against venoms with post-synaptic neurotoxic activity (TCAV) cross-neutralised the post-synaptic activity of multiple snake venoms. Antivenoms raised against pre- and post-synaptic neurotoxic venoms (TNPAV, IPAV, APAV) cross-neutralised both activities of Asian and Australian venoms. While acknowledging the limitations of adding antivenom prior to venom in an in vitro preparation, cross-neutralization of neurotoxicity means that antivenoms from one region may be effective in other regions which do not have effective antivenoms. TCAV only neutralized post-synaptic neurotoxicity and is potentially useful in distinguishing pre-synaptic and post-synaptic effects in the chick biventer cervicis preparation.

ACS Style

Anjana Silva; Wayne C. Hodgson; Geoffrey K. Isbister. Cross-Neutralisation of In Vitro Neurotoxicity of Asian and Australian Snake Neurotoxins and Venoms by Different Antivenoms. Toxins 2016, 8, 302 .

AMA Style

Anjana Silva, Wayne C. Hodgson, Geoffrey K. Isbister. Cross-Neutralisation of In Vitro Neurotoxicity of Asian and Australian Snake Neurotoxins and Venoms by Different Antivenoms. Toxins. 2016; 8 (10):302.

Chicago/Turabian Style

Anjana Silva; Wayne C. Hodgson; Geoffrey K. Isbister. 2016. "Cross-Neutralisation of In Vitro Neurotoxicity of Asian and Australian Snake Neurotoxins and Venoms by Different Antivenoms." Toxins 8, no. 10: 302.

Randomized controlled trial
Published: 01 September 2016 in Toxicon
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The prevention of adverse drug reactions to antivenom serum poses a formidable challenge in the management of snakebite. Hydrocortisone is being used concurrently with antivenom in order to prevent these adverse drug reactions without a proven benefit. However, all previous studies seemed to ignore the testing of effectiveness of hydrocortisone therapy during its pharmacological effects, which come hours later. On this principle, we aimed to test the effectiveness of intravenous hydrocortisone given 2 h or more prior to the commencement of antivenom therapy to reduce adverse drug reactions to antivenom. In an open-labelled randomized controlled trial, patients with a history of snakebite were randomly assigned to receive either 500 mg intravenous hydrocortisone bolus given 2 h or more prior to antivenom therapy (Group A) or at the time of antivenom therapy (Group B). The primary endpoint was the reduction of adverse drug reactions to antivenom of any grade of severity within the first 48 h. This trial has been registered with the "Sri Lanka Clinical Trials Registry", number SLCTR/2010/005. A total of 236 patients were randomized to group A or Group B. In the group A, 38 participants received hydrocortisone 2 h before administration of antivenom whilst 33 received hydrocortisone less than 2 h before administration of antivenom. In the Group B, 84 participants received hydrocortisone at the time of antivenom therapy. In Group A (n, 38), and Group B (n, 84), 15 patients (39%) and 29 patients (35%) developed reactions respectively and the difference is not significant (p = 0.598). Moreover, hydrocortisone therapy did not significantly reduce the occurrence of antievnom reactions of any grade of severity. Further, it didn't delay the occurrence of antivenom reactions in patients who received hydrocortisone either more than 2 h or less than 2 h before the antivenom as opposed to the control group (group B). Intravenous hydrocortisone shows no difference in the timing, rate or severity of adverse drug reactions to antivenom when administered simultaneously and up to 4 h prior to antivenom.

ACS Style

Senanayake A.M. Kularatne; Kosala Weerakoon; Anjana Silva; Kalana Maduwage; Chamara Walathara; Ishani Rathnayake; Senal Medagedara; Ranjith Paranagama; Suresh Mendis; P.V.R. Kumarasiri. Efficacy of intravenous hydrocortisone administered 2–4 h prior to antivenom as prophylaxis against adverse drug reactions to snake antivenom in Sri Lanka: An open labelled randomized controlled trial. Toxicon 2016, 120, 159 -165.

AMA Style

Senanayake A.M. Kularatne, Kosala Weerakoon, Anjana Silva, Kalana Maduwage, Chamara Walathara, Ishani Rathnayake, Senal Medagedara, Ranjith Paranagama, Suresh Mendis, P.V.R. Kumarasiri. Efficacy of intravenous hydrocortisone administered 2–4 h prior to antivenom as prophylaxis against adverse drug reactions to snake antivenom in Sri Lanka: An open labelled randomized controlled trial. Toxicon. 2016; 120 ():159-165.

Chicago/Turabian Style

Senanayake A.M. Kularatne; Kosala Weerakoon; Anjana Silva; Kalana Maduwage; Chamara Walathara; Ishani Rathnayake; Senal Medagedara; Ranjith Paranagama; Suresh Mendis; P.V.R. Kumarasiri. 2016. "Efficacy of intravenous hydrocortisone administered 2–4 h prior to antivenom as prophylaxis against adverse drug reactions to snake antivenom in Sri Lanka: An open labelled randomized controlled trial." Toxicon 120, no. : 159-165.