ORCID Profile
0000-0002-9968-3707
Current Organisations
Rajarata University of Sri Lanka Faculty of Medicine and Allied Sciences
,
Monash University
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Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.TOXICON.2022.03.014
Abstract: Russell's viper envenoming causes venom-induced consumption coagulopathy (VICC) within hours of a bite, which is associated with thrombotic microangiopathy (TMA) and acute kidney injury (AKI) in a proportion of cases. We report a juvenile Russell's viper bite in which a patient developed mild VICC after the usual 24-h observation period, which was subsequently associated with severe AKI due to TMA. This shows the clinical importance of detecting and treating mild VICC, which may be delayed or not detected with bedside clotting tests.
Publisher: Springer Science and Business Media LLC
Date: 27-12-2019
DOI: 10.1038/S41598-019-56643-0
Abstract: 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.) and E. 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.) and D. siamensis (100 µg/kg, i.v.) venoms caused ‘prolonged hypotension’, characterised by a persistent decrease in blood pressure with recovery. D. russelii venom (50 mg/kg and 100 mg/kg, i.m.) also caused prolonged hypotension. A priming dose of P. textilis venom (2 µg/kg, i.v.) prevented collapse by E. ocellatus venom (50 µg/kg, i.v.), but had no significant effect on subsequent addition of D. russelii venom (1 mg/kg, i.v). Two priming doses (1 µg/kg, i.v.) of E. ocellatus venom prevented collapse by E. ocellatus venom (50 µg/kg, i.v.). B. gabonica , C. vegrandis and B. arietans (all at 200 µg/kg, i.v.) induced mild transient hypotension. Artificial respiration prevented D. russelii venom induced prolonged hypotension but not rapid cardiovascular collapse from E. ocellatus venom. D. russelii venom (0.001–1 μg/ml) caused concentration-dependent relaxation (EC 50 = 82.2 ± 15.3 ng/ml, R max = 91 ± 1%) in pre-contracted mesenteric arteries. In contrast, E. ocellatus venom (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.
Publisher: Wiley
Date: 21-03-2017
Publisher: Frontiers Media SA
Date: 07-03-2022
Abstract: Venom-induced consumption coagulopathy (VICC) is an important clinical consequence of Russell’s viper ( Daboia russelii ) envenoming. There is limited evidence for antivenom effectiveness in resolving VICC. We aimed to compare the recovery of VICC in patients who received and did not receive antivenom following Russell’s viper envenoming. This was a non-randomized observational study comparing patients with VICC from Russell’s viper envenoming given antivenom for systemic envenoming and those not given antivenom. Antivenom administration was decided by the treating physicians. We included 44 patients with confirmed Russell’s viper bites with one or more International Normalized Ratio (INR) value ≥ 1.5 (VICC). We compared five patients who did not receive antivenom with 39 patients who did receive antivenom. The primary outcome was the proportion of patients with an INR & 1.5 by 48 h post-bite. The antivenom group had higher peak serum venom concentrations [median (IQR) = 272 (96–1,076) ng/mL versus 21 (8–58) ng/mL] and more severe VICC compared to the no antivenom group. Twenty seven of 39 patients (69%) in the antivenom group had an INR & 1.5 at 48 h post-bite compared to none of the five patients (0%) in the no antivenom group (absolute difference: 69% 95%CI: 13 to 83% p = 0.006 Fisher’s exact test). The fibrinogen recovered in 32 of 39 patients (82%) in the antivenom group compared to one of five patients (20%) in the no antivenom group (absolute difference 62% 95% CI: 28 to 95% p = 0.001 Fisher’s exact test). Both INR and fibrinogen were significantly improved between 24 and 48 h post-bite in the antivenom group compared to the no antivenom group. Antivenom accelerated the recovery of VICC in patients with Russell’s viper envenoming, compared to no recovery in a smaller group of patients with milder VICC not receiving antivenom. This supports the efficacy of antivenom in patients with VICC.
Publisher: Springer Science and Business Media LLC
Date: 29-08-2012
Publisher: Public Library of Science (PLoS)
Date: 30-11-2020
DOI: 10.1371/JOURNAL.PNTD.0008914
Abstract: 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 .0001]). A significantly greater proportion of transferred patients had features of systemic envenoming on admission compared to those directly admitted (166/212 [78%] versus 5/43 [12%] p .0001), and had positive clotting tests on admission (123/212 [58%] versus 10/43 [23%] p .0001). Sri Lankan snakebite patients present early to hospital, but there remains a delay until antivenom administration. This delay reflects a delay in the appearance of observable or measurable features of envenoming and a lack of reliable early diagnostic tests. Improved early antivenom treatment will require reliable, rapid diagnostics for systemic envenoming.
Publisher: Elsevier BV
Date: 08-2018
Publisher: Frontiers Media SA
Date: 28-03-2022
DOI: 10.3389/FPHAR.2022.815079
Abstract: The Indian Cobra ( Naja naja ) is among the “Big Four” responsible for most of the snakebite envenoming cases in India. Although recent proteomic studies suggest the presence of postsynaptic neurotoxins in N. naja venom, little is known about the pharmacology of these toxins. We isolated and characterized α-Elapitoxin-Nn2a (α-EPTX-Nn2a 7020 Da) and α-Elapitoxin-Nn3a (α-EPTX-Nn3a 7807 Da), a short-chain and long-chain postsynaptic neurotoxin, respectively, which constitute 1 and 3% of N. naja venom. α-EPTX-Nn2a (100–300 nM) and α-EPTX-Nn3a (100–300 nM) both induced concentration-dependent inhibition of indirect twitches and abolished contractile responses of tissues to exogenous acetylcholine and carbachol, in the chick biventer cervicis nerve-muscle preparation. The prior incubation of tissues with Indian polyvalent antivenom (1 ml/0.6 mg) prevented the in vitro neurotoxic effects of α-EPTX-Nn2a (100 nM) and α-EPTX-Nn3a (100 nM). The addition of Indian polyvalent antivenom (1 ml/0.6 mg), at the t 90 time point, could not reverse the in vitro neurotoxicity of α-EPTX-Nn2a (100 nM). The in vitro neurotoxicity of α-EPTX-Nn3a (100 nM) was partially reversed by the addition of Indian polyvalent antivenom (1 ml/0.6 mg), as well as repeated washing of the tissue. α-EPTX-Nn2a displayed non-competitive antagonism of concentration-response curves to carbachol, with a pA 2 of 8.01. In contrast, α-EPTX-Nn3a showed reversible antagonism of concentration-response curves to carbachol, with a pA 2 of 8.17. De novo sequencing of α-EPTX-Nn2a and α-EPTX-Nn3a showed a short-chain and long-chain postsynaptic neurotoxin, respectively, with 62 and 71 amino acids. The important observation made in this study is that antivenom can reverse the neurotoxicity of the clinically important long-chain neurotoxin, but not the short-chain neurotoxin, from N. naja venom.
Publisher: Sri Lanka Journals Online
Date: 09-2023
Publisher: MDPI AG
Date: 31-10-2020
Abstract: 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.
Publisher: MDPI AG
Date: 19-04-2017
Publisher: Frontiers Media SA
Date: 03-02-2022
Publisher: Sri Lanka Journals Online (JOL)
Date: 23-03-2022
Publisher: Springer Science and Business Media LLC
Date: 02-08-2018
Publisher: Informa UK Limited
Date: 02-11-2022
DOI: 10.1080/15563650.2022.2128816
Abstract: The whole blood clotting test (WBCT) is commonly used for diagnosing venom-induced consumption coagulopathy (VICC) in resource-poor settings. We aimed to investigate the diagnostic accuracy of the WBCT and capillary blood clotting test (CBCT) for detecting VICC in viper envenoming in Sri Lanka. All confirmed snakebites admitted to Teaching Hospital Anuradhapura from July 2020 to June 2021 were included. On admission, WBCTs after 15, 20 and 25 min observation times (WBCT-15, WBCT-20 and WBCT-25) and CBCT observed in 30 s intervals (CBCT-t), 5 and 10 min CBCT (CBCT-5 and CBCT-10) were done. Blood was collected simultaneously for prothrombin time (PT)/international normalized ratio (INR) and plasma fibrinogen. We defined VICC as an INR >1.5 (Incomplete VICC = INR>1.5 and complete VICC = ≥3.0). A total of 272 confirmed snakebites (Russell's viper[76], hump-nosed viper[89], non-venomous snakes[51] and unidentified bites[56]) were recruited (median age: 42 y [interquartile range: 30- 53 y] 189 males [69%]). On admission, 82 (30%) had incomplete VICC (INR >1.5 and 6.25 min. WBCTs are poorly diagnostic for VICC in Russell's viper and hump-nosed viper envenoming, missing up to two-thirds of patients for some tests. The WBCT-15 was the best test, improving for more severe VICC and greater than 2 h post-bite.
Publisher: MDPI AG
Date: 28-04-2016
Publisher: MDPI AG
Date: 13-04-2022
Abstract: Despite antivenoms being the only established specific treatment for neuromuscular paralysis arising from snake envenoming, their ability to reverse the post-synaptic neurotoxicity in snake envenoming is poorly understood. We investigated the ability of five commercial antivenoms i.e., King cobra monovalent, Thai cobra monovalent, Thai neuro polyvalent, Indian polyvalent and Australian polyvalent antivenoms to reverse neurotoxicity induced by the venoms of King cobra (Ophiophagus hannah, 3 µg/mL), Indian cobra (Naja naja, 5 µg/mL) and Thai cobra (Naja kaouthia, 3 µg/mL) using the in vitro chick-biventer cervicis nerve–muscle preparation. All three venoms displayed post-synaptic neurotoxicity, which was prevented by all tested antivenoms (40 µL/mL) added to the bath prior to venom. All antivenoms partially reversed the established post-synaptic neuromuscular block after the addition of the three venoms during a 180 min observation period, but to varying degrees and at different rates. The neurotoxic effects of O. hannah venom recovered to a greater magnitude (based on twitch height restoration) and faster than the neurotoxicity of N. kaouthia venom, which recovered to a lower magnitude more slowly. The recovery of post-synaptic neurotoxicity by N. naja venom was hindered due to the likely presence of cytotoxins in the venom, which cause direct muscle damage. The observations made in this study provide further evidence that the commercial antivenoms are likely to actively reverse established α-neurotoxin-mediated neuromuscular paralysis in snake envenoming, and there is cross-neutralisation with different antivenoms.
Publisher: MDPI AG
Date: 30-07-2020
Abstract: 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 in idual coastal taipans Oxyuranus scutellatus from four localities on the north-east coast of Australia, spanning a distance of 2000 km. 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 in iduals 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 in iduals from each population when making inter-specific comparisons.
Publisher: Springer Science and Business Media LLC
Date: 18-10-2013
Publisher: Springer Science and Business Media LLC
Date: 12-09-2012
Publisher: Elsevier BV
Date: 07-2014
Publisher: Informa UK Limited
Date: 28-11-2022
DOI: 10.1080/15563650.2022.2147843
Abstract: There is limited information on the risk of chronic kidney disease (CKD) following snakebite and its relationship with chronic interstitial nephritis in agricultural communities (CINAC). We aimed to investigate CKD in patients with a confirmed snakebite in rural Sri Lanka. Patients prospectively recruited to the Anuradhapura snakebite cohort with authenticated bites were followed up. Two groups of patients were followed up: 199 patients in group I with a snakebite (August 2013-October 2014), reviewed after 4 years, and 168 patients in group II with a snakebite (May 2017-August 2018), reviewed after one year, with serum creatinine (estimated glomerular filtration rate [eGFR]) and urinary albumin to creatinine ratio (ACR). There were 12/199 (6%) in group I and 9/168 (5%) in group II with AKI following snakebite 3/12 in group I and 2/9 in group II had haemodialysis. On review after 1 and 4 years, no patient had CKD and all had an eGFR ≥60 mL/min/1.73m There was no significant association between snakebite-associated AKI and CKD in patients followed up from a snakebite cohort post-bite. Microalbuminuria was common in these patients but likely associated with hypertension, diabetes mellitus and CINAC in this rural farming population.
Publisher: Frontiers Media SA
Date: 07-03-2022
DOI: 10.3389/FPHAR.2022.815069
Abstract: The King Cobra ( Ophiophagus hannah ) is the world’s largest venomous snake and has a widespread geographical distribution throughout Southeast Asia. Despite proteomic studies indicating the presence of postsynaptic neurotoxins in O. hannah venom, there are few pharmacological investigations of these toxins. We isolated and characterized α-elapitoxin-Oh3a (α-EPTX-Oh3a 7,938 Da), a long-chain postsynaptic neurotoxin, which constitutes 5% of O. hannah venom. α-EPTX-Oh3a (100–300 nM) caused concentration-dependent inhibition of indirect twitches and inhibited contractile responses of tissues to exogenous acetylcholine and carbachol, in the chick biventer cervicis nerve-muscle preparation. The prior incubation of tissues with Thai Red Cross Society King Cobra antivenom (1 ml/0.8 mg) prevented the in vitro neurotoxic effects of α-EPTX-Oh3a (100 nM). The addition of Thai Red Cross Society King Cobra antivenom (1 ml/0.8 mg), at the t 90 time point partially reversed the in vitro neurotoxicity of α-EPTX-Oh3a (100 nM). Repeatedly washing the tissue did not allow significant recovery from the in vitro neurotoxic effects of α-EPTX-Oh3a (100 nM). α-EPTX-Oh3a demonstrated pseudo-irreversible antagonism of concentration-response curves to carbachol, with a pA 2 of 8.99. De novo sequencing of α-EPTX-Oh3a showed a long-chain postsynaptic neurotoxin with 72 amino acids, sharing 100% sequence identity with Long neurotoxin OH-55. In conclusion, the antivenom is useful for reversing the clinically important long-chain α-neurotoxin-mediated neuromuscular paralysis.
Publisher: Sri Lanka Journals Online (JOL)
Date: 03-04-2013
Abstract: The morphology of hemipenes, the male external genitalia of reptiles, is considered to be a character of taxonomic importance. It has, however, until recently been used only rarely in agamid systematics. Phylogenies of Sri Lankan Agamidae, constructed using mitochondrial DNA and hemipeneal morphology, have shown remarkable convergence, highlighting the importance of hemipeneal morphology in the taxonomy of these lizards. Here we present descriptions and illustrations of the hemipenes of 17 of the 18 species of Sri Lankan Agamidae and provide a key to the identification of species groups based on this character. Ceylon Journal of Science (Bio. Sci.) 41 (2): 111-123, 2012 DOI: 0.4038/cjsbs.v41i2.5381
Publisher: Public Library of Science (PLoS)
Date: 26-02-2014
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1016/J.JFLM.2013.09.009
Abstract: A 19 year old male was admitted to a tertiary care centre in Sri Lanka, with a history of snake bite while sleeping at night. A killed specimen of a snake was brought with the patient. It had been identified as a non-venomous snake by the doctor and handed over to relatives, with a comment to that effect. Patient had no clinical or laboratory evidence of envenoming on admission. Patient developed bilateral ptosis six hours after alleged snake bite, soon followed by respiratory paralysis and was treated with Indian polyvalent anti-venom serum. After 12 h of the bite, patient had developed hypotension that did not respond to ionotropes. Despite intensive management, patient had become deeply comatose and deceased 46 h following the snake bite. Autopsy revealed features suggestive of disseminated intravascular coagulation. Since an allegation of medical negligence too had been levelled by the relations of the patient against the clinical staff, the buried specimen of the snake was recovered by police, on a judicial order, a week later. It was found to be almost completely disintegrated and only the scales and bones were remaining. According to the scale characters, the reconstructed specimen was identified as Indian krait (Bungarus caeruleus). Authentication of snake is important in investigating a death due to snake bite, especially when the snake was initially claimed to be a non-venomous snake. This case suggests the usefulness of forensic identification of species of the snake in investigating suspected snake bite cases.
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.TOXICON.2016.08.011
Abstract: 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.
Publisher: Informa UK Limited
Date: 29-02-2016
DOI: 10.3109/15563650.2016.1143556
Abstract: Russell's viper is more medically important than any other Asian snake, due to number of envenoming's and fatalities. Russell's viper populations in South India and Sri Lanka (Daboia russelii) cause unique neuromuscular paralysis not seen in other Russell's vipers. To investigate the time course and severity of neuromuscular dysfunction in definite Russell's viper bites, including antivenom response. We prospectively enrolled all patients (>16 years) presenting with Russell's viper bites over 14 months. Cases were confirmed by snake identification and/or enzyme immunoassay. All patients had serial neurological examinations and in some, single fibre electromyography (sfEMG) of the orbicularis oculi was performed. 245 definite Russell's viper bite patients (median age: 41 years 171 males) presented a median 2.5 h (interquartile range: 1.75-4.0 h) post-bite. All but one had local envenoming and 199 (78%) had systemic envenoming: coagulopathy in 166 (68%), neurotoxicity in 130 (53%), and oliguria in 19 (8%). Neurotoxicity was characterised by ptosis (100%), blurred vision (93%), and ophthalmoplegia (90%) with weak extraocular movements, strabismus, and diplopia. Neurotoxicity developed within 8 h post-bite in all patients. No bulbar, respiratory or limb muscle weakness occurred. Neurotoxicity was associated with bites by larger snakes (p < 0.0001) and higher peak serum venom concentrations (p = 0.0025). Antivenom immediately decreased unbound venom in blood. Of 52 patients without neurotoxicity when they received antivenom, 31 developed neurotoxicity. sfEMG in 27 patients with neurotoxicity and 23 without had slightly elevated median jitter on day 1 compared to 29 normal subjects but normalised thereafter. Neurological features resolved in 80% of patients by day 3 with ptosis and weak eye movements resolving last. No clinical or neurophysiological abnormality was detected at 6 weeks or 6 months. Sri Lankan Russell's viper envenoming causes mild neuromuscular dysfunction with no long-term effects. Indian polyvalent antivenom effectively binds free venom in blood but does not reverse neurotoxicity.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.TOXICON.2019.03.015
Abstract: 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.
Publisher: MDPI AG
Date: 26-04-2022
Abstract: We studied the neutralisation of Sri Lankan Russell’s viper (Daboia russelii) and Australian mulga snake (Pseudechis australis) venom-induced myotoxicity by Indian (Vins and Bharat) and Australian (Seqirus) polyvalent antivenoms, using the in vitro chick biventer skeletal muscle preparation. Prior addition of Bharat or Vins antivenoms abolished D. russelii venom (30 µg/mL)-mediated inhibition of direct twitches, while Australian polyvalent antivenom was not protective. Bharat antivenom prevented, while Vins and Australian polyvalent antivenoms partially prevented, the inhibition of responses to exogenous KCl. Myotoxicity of Mulga venom (10 µg/mL) was fully neutralised by the prior addition of Australian polyvalent antivenom, partially neutralised by Vins antivenom but not by Bharat antivenom. Although the myotoxicity of both venoms was partially prevented by homologous antivenoms when added 5 min after the venom, with an increasing time delay between venom and antivenom, the reversal of myotoxicity gradually decreased. However, antivenoms partially prevented myotoxicity even 60 min after venom. The effect of antivenoms on already initiated myotoxicity was comparable to physical removal of the toxins by washing the bath at similar time points, indicating that the action of the antivenoms on myotoxicity is likely to be due to trapping the toxins or steric hindrance within the circulation, not allowing the toxins to reach target sites in muscles.
Publisher: MDPI AG
Date: 18-10-2016
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.WEM.2013.10.009
Abstract: Although snake bite remains a major health problem in Sri Lanka, there is a dearth of baseline information that would be useful in education about and prevention of snakebite. The purpose of this study was to describe the socio-demographic characteristics, behavioral responses, treatment seeking, and prehospital interventions of snakebite victims in an area with high snakebite burden. This prospective study was based on a cohort of snakebite victims presented to the Anuradhapura Teaching Hospital over a 1-year period from January 2010. Of the total of 1018 snakebite admissions, 69% were male and 65.8% were aged 21 to 50 years. Most of the victims were farmers (40%). The offending snakes were seen by 549 victims (54%) of these, only 46% (255) presented with a dead snake specimen. Only 38 of 1018 (4%) had first sought some form of indigenous treatment such as locally applied medications, herbal decoctions, nasal insufflations ("Nasna"), or applying snake stone over the bitten site. Some form of first aid had been adopted by 681 victims (67%), of whom all had washed the bitten site, and 18 victims (2%) and 4 (0.4%) had applied a dressing or incised the bitten site, respectively. A tourniquet had been applied by 353 victims (35%) for mean duration of 26 minutes (range, 5 to 120 minutes). None of the patients had immobilized the bitten limb by splinting. Oral medications had been used for pain relief in 74 cases (7%), paracetamol by all. A proportion of patients still seek native remedies and use inappropriate first aid after snakebite in Sri Lanka.
Publisher: Sri Lanka Journals Online (JOL)
Date: 21-07-2023
Abstract: No abstract available
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.TOXICON.2012.10.013
Abstract: Hump-nosed pit vipers of Genus Hypnale are the commonest cause of snake bite in Sri Lanka. Although there are many reports of local effects, coagulopathy and acute kidney injury, it remains unclear how frequent these clinical effects are and therefore the medical importance of this snake genus. The genus has been recently revised to include Hypnale hypnale from Sri Lanka and Western Ghats of Southern India, and the two endemic species to Sri Lanka, Hypnale zara and Hypnale nepa. This was a prospective hospital-based clinical study of definite Hypnale spp. bites from July 2008 to July 2010 in six Sri Lankan hospitals. There were 114 patients included and all snakes were correctly identified by hospital staff as Hypnale spp. Of these, 93 snakes were identified as H. hypnale by an expert, 16 as H. zara and five as H. nepa. Most bites occurred on the lower limbs in the daytime. There was no difference in the clinical effects between the three species. Pain and fang marks were present in all patients, 101 had local swelling and only 16 (14%) developed extensive local swelling that spread proximally and involved more than half of the bitten limb. Systemic symptoms occurred in 18 patients four patients had an abnormal 20 min whole blood clotting test and one patient developed an acute kidney injury that required haemodialysis. All patients were discharged alive with a median length of stay of 2 days. This study confirms that hump-nosed viper bites cause only minor effects in most cases. Future studies need to undertake formal coagulation studies and identify important early indicators of renal impairment.
Publisher: Medknow
Date: 2023
Publisher: MDPI AG
Date: 31-03-2019
Abstract: 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 utations, 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.
Publisher: Sri Lanka Journals Online (JOL)
Date: 21-07-2023
Abstract: This perspective highlights the misidentifications of medically important snakes that could commonly occur in hospitals and provides a quick-reference, illustrated guide for minimising such snake misidentifications in the Sri Lankan healthcare setting.
Publisher: Springer Science and Business Media LLC
Date: 27-05-2016
DOI: 10.1038/SREP26778
Abstract: In vitro antivenom efficacy studies were compared to rodent lethality studies to test two Indian snake antivenoms (VINS and BHARAT) against four Sri Lankan snakes. In vitro efficacy was tested at venom concentrations consistent with human envenoming. Efficacy was compared statistically for one batch from each manufacturer where multiple vials were available. In binding studies EC 50 for all VINS antivenoms were less than BHARAT for D. russelii [553 μg/mL vs. 1371 μg/mL = 0.016), but were greater for VINS antivenoms compared to BHARAT for N. naja [336 μg/mL vs. 70 μg/mL 0.0001]. EC 50 of both antivenoms was only slighty different for E. carinatus and B. caeruleus . For procoagulant activity neutralisation, the EC 50 was lower for VINS compared to BHARAT - 60 μg/mL vs. 176 μg/mL (p 0.0001) for Russell’s viper and 357 μg/mL vs. 6906μg/mL (p 0.0001) for Saw-scaled viper. Only VINS antivenom neutralized in vitro neurotoxicity of krait venom. Both antivenoms partially neutralized cobra and didn’t neutralize Russell’s viper neurotoxicity. Lethality studies found no statistically significant difference in ED 50 values between VINS and BHARAT antivenoms. VINS antivenoms appeared superior to BHARAT at concentrations equivalent to administering 10 vials antivenom, based on binding and neutralisation studies. Lethality studies were inconsistent suggesting rodent death may not measure relevant efficacy outcomes in humans.
Publisher: Informa UK Limited
Date: 23-07-2013
DOI: 10.3109/15563650.2013.811589
Abstract: Limited information exists on the coagulopathy caused by hump-nosed pit viper (Hypnale hypnale) envenoming. This study aimed to characterise the coagulopathy in hump-nosed pit viper bites by measuring laboratory clotting times and factor studies. Cases of hump-nosed pit viper envenoming were included from a prospective cohort study of Sri Lankan snake-bite patients. Patient age, sex, snake identification, time of bite and clinical effects were recorded. Patients did not receive anti-venom because no specific anti-venom to hump-nosed vipers exists. All patients received supportive care and serial 20-min whole blood clotting tests (WBCT20). The prothrombin time (PT), international normalised ratio (INR), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, von Willebrand factor (vWF) antigen and D-Dimer concentrations were measured. The median of highest or lowest test result for each patient was reported with interquartile range (IQR). Results. There were 80 hump-nosed pit viper bites, median age was 37 years (IQR: 26-51 years) and 48 were male. The WBCT20 was positive in one patient. The median highest INR was 1.9 (1.5-2.2 Range: 1.3 to > 12) and median highest aPTT was 54 s (46-72 s Range: 35-170 s). There was low fibrinogen [median: 1.3 g/L , -1.8 g/L Range: < 0.2-2.9], low factor VIII levels [median: 23% 16-37%] and low factor V levels [median: 43% 23-74%]. D-Dimer concentrations [median: 3.4 mg/L 2-7.4 mg/L] were slightly elevated. Factors II, VII and X and vWF antigen concentrations were normal. Hump-nosed pit viper bites result in a mild coagulopathy which is usually not detected by a WBCT20. It is characterised by mild elevation of INR, low fibrinogen and Factors V and VIII which may be consistent with the venom containing a thrombin-like enzyme.
Publisher: Public Library of Science (PLoS)
Date: 02-12-2016
Publisher: Public Library of Science (PLoS)
Date: 09-2022
DOI: 10.1371/JOURNAL.PNTD.0010723
Abstract: The acute effects of snakebite are often emphasized, with less information on long-term effects. We aimed to describe the long-term health effects perceived by patients followed up after confirmed snakebites. Two groups of snakebite patients ( y) from the Anuradhapura snakebite cohort were reviewed: Group I had a snakebite during August 2013-October 2014 and was reviewed after 4 years, and group II had a snakebite during May 2017-August 2018, and was reviewed after one year. Patients were invited by telephone, by sending letters, or doing home visits, including 199 of 736 patients (27%) discharged alive from group I and 168 of 438 patients (38%) from group II, a total of 367 followed up. Health effects were categorised as musculoskeletal, impact on daily life, and medically unexplained. Health issues were attributed to snakebite in 107/199 patients (54%) from group I and 55/168 patients (33%) from group II, suggesting the proportion with health issues increases with time. Sixteen patients (all viperine bites) had permanent musculoskeletal problems, none with a significant functional disability affecting daily routine. 217/367 reported being more vigilant about snakes while working outdoors, but only 21/367 were using protective footwear at review. Of 275 farmers reviewed, only six (2%) had restricted farming activities due to fear of snakebite, and only one stopped farming. 104/199 (52%) of group I and 42/168 (25%) of group II attributed non-specific symptoms (fatigue, body aches, pain, visual impairment) and/or oral cavity-related symptoms (avulsed teeth, loose teeth, receding gums) to the snakebite, which cannot be explained medically. In multivariate logistic regression, farming, type of snake, antivenom administration, and time since snakebite were associated with medically unexplained symptoms. The latter suggests medically unexplained effects increased with time. Based on two groups of snakebite patients reviewed one and four years post-bite, we show that long-term musculoskeletal disabilities are uncommon and not severe in snakebite survivors in rural Sri Lanka. However, a large portion of patients complain of various non-specific general and oral symptoms, not explainable based on the known pathophysiology of snakebite. These perceived effects of snakebite were more common in patients with systemic envenoming, and were more frequent the longer the time post-bite.
Publisher: Public Library of Science (PLoS)
Date: 02-2016
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 08-2018
DOI: 10.1007/S00018-018-2893-X
Abstract: 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.
Publisher: MDPI AG
Date: 26-04-2021
Abstract: 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.
Publisher: Informa UK Limited
Date: 03-07-2023
Publisher: Springer Science and Business Media LLC
Date: 11-07-2016
DOI: 10.1007/S12640-016-9650-4
Abstract: Russell's vipers are snakes of major medical importance in Asia. Russell's viper (Daboia russelii) envenoming in Sri Lanka and South India leads to a unique, mild neuromuscular paralysis, not seen in other parts of the world where the snake is found. This study aimed to identify and pharmacologically characterise the major neurotoxic components of Sri Lankan Russell's viper venom. Venom was fractionated using size exclusion chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). In vitro neurotoxicities of the venoms, fractions and isolated toxins were measured using chick biventer and rat hemidiaphragm preparations. A phospholipase A
Publisher: Springer Science and Business Media LLC
Date: 2014
Publisher: Public Library of Science (PLoS)
Date: 12-12-2022
DOI: 10.1371/JOURNAL.PONE.0278920
Abstract: Human intestinal nematode infections are a global public health issue as they can result in considerable morbidity in infected in iduals, mainly in developing countries. These infections continue to go undiagnosed, as they tend to be mainly endemic in resource-poor communities where there is a shortage of experienced laboratory staff and relevant diagnostic technologies. This is further exacerbated by the nature of intermittent shedding of eggs and larvae by these parasites. Diagnostic methods range from simple morphological identification to more specialised high-throughput sequencing technologies. Microscopy-based methods, although simple, are labour-intensive and considerably less sensitive than molecular methods which are rapid and have high levels of accuracy. Molecular methods use nucleic acid lification (NAA) to lify the deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) fragments of the parasite to detect and determine its presence using different technologies (NAAT). They have increased the sensitivity of detection and quantitation of intestinal nematode infections, especially in low infection intensity settings. The absence of a gold standard test limits current diagnosis and, in turn, restricts intervention measures and effective control efforts. The objective of this review is to determine the accuracy of NAATs in detecting human intestinal nematode infections using Kato-Katz as the reference test for the most common soil-transmitted helminth (STH) infections and the scotch tape test for enterobiasis and Baermann method for strongyloidiasis. Relevant studies will be identified by searches in electronic databases. Two reviewers will independently screen the literature against eligibility criteria. The methodological quality of studies will then be appraised by two reviewers using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Discrepancies will be addressed by a third reviewer. The true positives, false positives, true negatives and false negatives of all the studies will be extracted into contingency tables. In paired forest plots, study-specific sensitivity and specificity with a 95 per cent confidence interval will be displayed. The systematic review of this protocol will report the diagnostic accuracy of currently available NAATs for the detection of human intestinal nematode infections. This will help healthcare providers and administrators determine the diagnostic method to be used in different clinical and preventive settings. Trial registration : PROSPERO registration number for this protocol is CRD42022315730 .
Publisher: Sri Lanka Journals Online (JOL)
Date: 15-07-2022
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.WEM.2013.01.008
Abstract: Flying snakes (Genus Chrysopelea) are a group of ophisthoglyphous colubrids in South and South East Asia known for gliding in the air. Of the five species of flying snakes, Sri Lankan flying snake, Chrysopelea taprobanica, is endemic to Sri Lanka. Authenticated bites and the venom characteristics of this uncommon snake remain unknown. We report the first authenticated case of C taprobanica bite, in which a 45-year-old woman had signs of mild local envenoming after the bite, with no evidence of systemic envenoming.
Publisher: Informa UK Limited
Date: 2019
Publisher: MDPI AG
Date: 10-09-2020
Abstract: 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 erse snake species. Venous clotting time is almost exclusively used in Thailand. Many validation studies have methodological limitations, including small s le 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.
Publisher: Portland Press Ltd.
Date: 20-03-2020
DOI: 10.1042/BST20190739
Abstract: 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.
Publisher: Sri Lanka Journals Online (JOL)
Date: 15-03-2022
Publisher: Springer Science and Business Media LLC
Date: 2014
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.TOXICON.2022.09.006
Abstract: Kounis syndrome is the occurrence of acute coronary syndrome associated with mast cell and platelet activation in the setting of allergic or anaphylactic insults. Kounis syndrome has been previously reported following snake envenoming rarely, with or without antivenom therapy. We report a case of inferolateral ST elevation myocardial infarction 32 hours from a confirmed Russell's viper bite. He also had an anaphylactic reaction soon after antivenom. The absence of underlying atheromatous coronary artery disease during subsequent cardiac imaging was suggestive of a diagnosis of a type I variant of Kounis syndrome. Chest pain completely resolved by day 6 following initiation of standard treatment for acute coronary syndrome. Concurrence of allergic features and acute coronary syndrome in a snakebite patient following antivenom therapy should alert clinicians to the possibility of Kounis syndrome, which should be diagnosed with a high degree of clinical suspicion.
Location: Sri Lanka
No related grants have been discovered for Anjana Silva.