First aid and pre-hospital practices in snakebite victims: The persistent use of harmful interventions.

First aid intervention and pre-hospital (FAPH) practices are common in patients suffering from snakebite envenomation (SBE). In this study, we have reviewed the literature concerning the use of these practices in various regions of the world in the period 1947-2023 based on published prospective studies. A total of 71 publications fulfilled the inclusion criteria. In terms of the total number of patients in all studies that used each FAPH intervention, the most common practice was the application of tourniquets (45.8%). Other FAPH practices described include cuts/incisions (6.7%), the application of a variety of natural or synthetic substances at the bite site (5.6%), and ingestion of natural, usually herbal, remedies (2.9%). Washing the site of the bite was described in 9.1% of patients. There were other less frequent FAPH practices, including suction, splinting-immobilization, pressure-bandage, ice packs, application of a snake/black stone, and administration of alcoholic beverages. There were differences in the extent of application of FAPH interventions in different continents. Tourniquets were highest (55.7%) in Asia. Topical application of various products was common in South America, while pressure-bandage was only reported in Australia. We did not find any statistically significant variations in the frequency of the most frequent FAPH interventions at three-time intervals (before 2006, between 2006 and 2015, and after 2015). Our findings highlight the use of FAPH interventions in patients suffering SBE, some of which are known to be harmful. It is necessary to study these practices to a higher level of geographic granularity, using community-based surveys. Programs tailored to local contexts should be promoted, aimed at avoiding the use of harmful FAPH practices. It is also necessary to assess the efficacy and safety of some interventions through robust preclinical and clinical studies.

The Role of Serum NT-proBNP for Predicting Left Ventricular Systolic Dysfunction in Hospitalized Patients in Sri Lanka.

Background/aims: Only a few studies have addressed the role of NT-proBNP in identifying Left Ventricular Systolic Dysfunction (LVSD) in South Asian populations. Therefore, the current study was aimed at assessing the use of serum NT-proBNP in predicting LVSD in a hospitalized population in Sri Lanka. Methods: A random sample of 278 individuals referred for echocardiography at a major Teaching Hospital consented for venous blood samples to be collected for serum NT-proBNP assay by sandwich ELISA. Based on the ejection fraction (LVEF) and fractional shortening (FS), participants were differentiated as LVSD (LVEF<50%, FS≤ 29%) and non-LVSD individuals (LVEF>60%). According to inclusion/exclusion criteria, the final study sample consisted of 100 LVSD patients and 41 non-LVSD individuals. Results: The mean ages of the LVSD and non-LVSD groups were 69.1 (±6.2 years) and 71.4 (±2.4 years) (p=0.066) respectively. The median NT-proBNP value (with IQR) among LVSD patients (528.2 pg/mL,355.2-924.2) was comparatively higher than that of non-LVSD individuals (207.3 pg/mL,177.5-343.0). Strong correlations of NT-proBNP level with LVEF (Spearman rho= -0.84, p<0.001) and FS (rho= -0.81, p<0.001) suggested that serum NT-proBNP concentration increases in parallel to deteriorating left ventricular functions. The AUROC of serum NT-proBNP for differentiating LVSD was 0.859 (95% CI:0.79 - 0.92) and the optimal cut-off level for predicting LVSD was 265pg/mL, with 90% sensitivity and 70% specificity. Conclusion: Current Sri Lankan study revealed a considerable correlation of serum NT-proBNP level with LVSD and utilizing such an assay for screening will facilitate adequate evidence to rule-out LVSD among high-risk residents.

Indian Polyvalent Antivenom Accelerates Recovery From Venom-Induced Consumption Coagulopathy (VICC) in Sri Lankan Russell's Viper (Daboia russelii) Envenoming.

Background: 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. Patients and Methods: 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. Results: 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. Conclusion: 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.

Web-based snake identification service: A successful model of snake identification in Sri Lanka.

Snakes are reptiles of great biomedical significance. The accurate identification of snakes is particularly important for healthcare workers to diagnose and treat victims of snakebite envenoming. Further, snake identification is vital for the general population, especially to those who live in areas of high snakebite incidence. Owing to the great diversity of snakes and the superficial similarities between some species, the correct identification of these reptiles is often difficult. Therefore, identification of snake species is challenging for healthcare workers, biologists, naturalists, and the general population. To overcome this challenge, we developed a web-based snake identification service (www.snakesidentification.org) in Sri Lanka, which provides rapid and accurate identification by experienced herpetologists. This service received 486 identification requests over a period of 40 months. The majority of requests were from Colombo District [140 (28.8%)], though only 63 (13.0%) of these were identified as medically important snakes. The majority [389 (80.0%)] of the requests related either to feebly venomous colubrid snakes or non-venomous species. The sample included 30 (of 107) snake species in the island, including 8 endemic species. There were 315 (64.8%) requests relating to live snakes. In the majority of cases (285, 90.4%), the snake was released to the closest available habitat after being identified. The median time taken to respond to requests was 70 min (interquartile range 23-299 min). The majority of persons making requests (283, 58.2%) were unable to identify the snakes. For those who attempted identification the snakes, correct identification was made by only 59 (12.1%), whereas 144 (29.6%) identified the snake incorrectly. This web-based snake identification service provides an example of a successful and useful model of rapid snake identification. Similar models could be implemented in other regions and countries to provide accurate information on snake identification both to the healthcare workers and the general public.

Snakebite envenoming in different national contexts: Costa Rica, Sri Lanka, and Nigeria.

Snakebite envenoming is a neglected tropical disease that predominantly affects impoverished rural communities in sub-Saharan Africa, Asia, and Latin America. The global efforts to reduce the impact of this disease must consider the local national contexts and, therefore, comparative studies on envenomings in different countries are necessary to identify strengths, weaknesses and needs. This work presents a comparative analysis of snakebite envenomings in Costa Rica, Sri Lanka, and Nigeria. The comparison included the following aspects: (a) burden of envenomings, (b) historical background of national efforts to confront envenomings, (c) national health systems, (d) antivenom availability and accessibility including local production, (e) training of physicians and nurses in the diagnosis and management of envenomings, (f) prevention campaigns and community-based work, (g) scientific and technological platforms in these topics, and (h) international cooperation programs. Strengths and weaknesses were identified in the three contexts and several urgent tasks to improve the management of this disease in these countries are highlighted. This comparative analysis could be of benefit for similar studies in other national and regional contexts.

Snake bite associated with acute kidney injury.

Acute kidney injury (AKI) is a well-known life-threatening systemic effect of snake envenomation which commonly happens secondary to snake bites from families of Viperidae and Elapidae. Enzymatic toxins in snake venom result in injuries to all kidney cell types including glomerular, tubulo-interstitial and kidney vasculature. Pathogenesis of kidney injury due to snake envenomation includes ischaemia secondary to decreased kidney blood flow caused by systemic bleeding and vascular leakage, proteolytic degradation of the glomerular basement membrane by snake venom metalloproteinases (SVMPs), deposition of microthrombi in the kidney microvasculature (thrombotic microangiopathy), direct cytotoxic action of venom, systemic myotoxicity (rhabdomyolysis) and accumulation of large amounts of myoglobin in kidney tubules. Clinical features of AKI include fatigue, loss of appetite, headache, nausea, vomiting, oliguria and anuria. Monitoring of blood pressure, fluid balance, serum creatinine, blood urea nitrogen and serum electrolytes is useful in managing AKI induced by snake envenomation. Early initiation of anti-snake venom and early diagnosis of AKI are always desirable. Biomarkers which will help in early prediction of AKI are being explored, and current studies suggest that urinary clusterin, urinary neutrophil gelatinase-associated lipocalin, and serum cystatin C may play an important clinical role in the future. Apart from fluid and electrolyte management, kidney support including early and prompt initiation of kidney replacement therapy when indicated forms the bedrock in managing snake bite-associated AKI. Long-term follow-up is important because of chances of progression towards CKD.

Paediatric snakebite envenoming: recognition and management of cases.

Snakebite in children can often be severe or potentially fatal, owing to the lower volume of distribution relative to the amount of venom injected, and there is potential for long-term sequelae. In the second of a two paper series, we describe the pathophysiology of snakebite envenoming including the local and systemic effects. We also describe the diagnosis and management of snakebite envenoming including prehospital first aid and definitive medical and surgical care.

Second case report of slender coral snake (Calliophis melanurus sinhaleyus) envenomation of Sri Lanka.

Bite and envenomation by the slender coral snake (Calliophis melanurus sinhaleyus) is rare in Sri Lanka. This case report describes an authenticated slender coral snake envenomation that occurred in a 32-year-old male. The bite to the middle phalanx of the left index finger was allowed to persist for 10 minutes. The victim developed pain, swelling and paresthesia without signs of systemic neurotoxicity.

Enzyme immunoassays for detection and quantification of venoms of Sri Lankan snakes: Application in the clinical setting.

BACKGROUND: Detection and quantification of snake venom in envenomed patients' blood is important for identifying the species responsible for the bite, determining administration of antivenom, confirming whether sufficient antivenom has been given, detecting recurrence of envenoming, and in forensic investigation. Currently, snake venom detection is not available in clinical practice in Sri Lanka. This study describes the development of enzyme immunoassays (EIA) to differentiate and quantify venoms of Russell's viper (Daboia russelii), saw-scaled viper (Echis carinatus), common cobra (Naja naja), Indian krait (Bungarus caeruleus), and hump-nosed pit viper (Hypnale hypnale) in the blood of envenomed patients in Sri Lanka. METHODOLOGY / PRINCIPAL FINDINGS: A double sandwich EIA of high analytical sensitivity was developed using biotin-streptavidin amplification for detection of venom antigens. Detection and quantification of D. russelii, N. naja, B. caeruleus, and H. hypnale venoms in samples from envenomed patients was achieved with the assay. Minimum (less than 5%) cross reactivity was observed between species, except in the case of closely related species of the same genus (i.e., Hypnale). Persistence/ recurrence of venom detection following D. russelii envenoming is also reported, as well as detection of venom in samples collected after antivenom administration. The lack of specific antivenom for Hypnale sp envenoming allowed the detection of venom antigen in circulation up to 24 hours post bite. CONCLUSION: The EIA developed provides a highly sensitive assay to detect and quantify five types of Sri Lankan snake venoms, and should be useful for toxinological research, clinical studies, and forensic diagnosis.

Paediatric snakebite envenoming: the world's most neglected 'Neglected Tropical Disease'?

Snakebite disproportionally affects children living in impoverished rural communities. The WHO has recently reinstated snakebites on its list of Neglected Tropical Diseases and launched a comprehensive Strategy for the Prevention and Control of Snakebite Envenoming. In the first of a two paper series, we describe the epidemiology, socioeconomic impact and key prevention strategies. We also explore current challenges and priorities including the production and distribution of safe and effective antivenom.

Early identification of acute kidney injury in Russell's viper (Daboia russelii) envenoming using renal biomarkers.

BACKGROUND: Acute kidney injury (AKI) is a major complication of snake envenoming, but early diagnosis remains problematic. We aimed to investigate the time course of novel renal biomarkers in AKI following Russell's viper (Daboia russelii) bites. METHODOLOGY/PRINCIPAL FINDINGS: We recruited a cohort of patients with definite Russell's viper envenoming and collected serial blood and urine samples on admission (<4h post-bite), 4-8h, 8-16h, 16-24h, 1 month and 3 months post-bite. AKI stage (1-3) was defined using the Acute Kidney Injury Network criteria. AKI stages (1-3) were defined by the Acute Kidney Injury Network (AKIN) criteria. There were 65 Russell's viper envenomings and 49 developed AKI: 24 AKIN stage 1, 13 stage 2 and 12 stage 3. There was a significant correlation between venom concentrations and AKI stage (p = 0.007), and between AKI stage and six peak biomarker concentrations. Although most biomarker concentrations were elevated within 8h, no biomarker performed well in diagnosing AKI <4h post-bite. Three biomarkers were superior to serum creatinine (sCr) in predicting AKI (stage 2/3) 4-8h post-bite: serum cystatin C (sCysC) with an area under the receiver operating curve (AUC-ROC), 0.78 (95%CI:0.64-0.93), urine neutrophil gelatinase-associated lipocalin (uNGAL), 0.74 (95%CI:0.59-0.87) and urine clusterin (uClu), 0.81 (95%CI:0.69-0.93). No biomarker was better than sCr after 8h. Six other urine biomarkers urine albumin, urine beta2-microglobulin, urine kidney injury molecule-1, urine cystatin C, urine trefoil factor-3 and urine osteopontin either had minimal elevation, and/or minimal prediction for AKI stage 2/3 (AUC-ROC<0.7). CONCLUSIONS/SIGNIFICANCE: AKI was common and sometimes severe following Russell's viper bites. Three biomarkers uClu, uNGAL and sCysC, appeared to become abnormal in AKI earlier than sCr, and may be useful in early identification of envenoming.

Nephrotoxicity induced by the venom of Hypnale hypnale from Sri Lanka: Studies on isolated perfused rat kidney and renal tubular cell lines.

The hump-nosed pit viper Hypnale hypnale is responsible for a high number of snakebite cases in southwestern India and Sri Lanka. Although most patients only develop local signs and symptoms of envenoming, there is a growing body of evidence indicating that these envenomings may be associated with systemic alterations, including acute kidney injury. In this study we evaluated the renal toxicity of H. hypnale venom by using a perfused isolated rat kidney system and by assessing cytotoxicity in two different renal tubular cell lines in culture. The venom caused alterations in several renal functional parameters, such as reduction on perfusion pressure, renal vascular resistance, and sodium and chloride tubular transport, whereas glomerular filtration rate and urinary flow initially decreased and then increased after venom perfusion. In addition, this venom was cytotoxic to proximal and distal renal tubular cells in culture, with predominance of necrosis over apoptosis. Moreover, the venom affected the mitochondrial membrane potential and induced an increment in reactive oxygen species in these cells. Taken together, our results demonstrate a nephrotoxic activity of H. hypnale venom in these experimental models, in agreement with clinical observations.

The identity of the Sri Lankan Amblypharyngodon (Teleostei, Cyprinidae).

Morphological and molecular analyses of specimens representative of the geographic range of the cyprinid genus Amblypharyngodon in Sri Lanka suggest the presence of only a single species in the island, for which the name Amblypharyngodongrandisquamis Jordan & Starks, 1917, is available. Amblypharyngodongrandisquamis is a species endemic to Sri Lanka, distributed across the lowlands of both of the island's main climatic zones. It is distinguished from all other species of Amblypharyngodon, including the three species recorded from peninsular India (A.mola, A.microlepis, and A.melettinus), by a suite of characters that includes a body depth of 26.9-31.2% of the standard length (SL), 42-56 scales in the lateral series (of which usually 8-16 are pored), 20-24 circumpeduncular scales, 14-17 scale rows between the origins of the dorsal and pelvic fins, a dorsal-fin height of 21.1-27.6% SL, 18-19 caudal vertebrae and an eye diameter of 22.7-30.5% of the head length. Amblypharyngodongrandisquamis differs from A.melettinus and A.mola by uncorrected pairwise genetic distances of more than 9% and 6%, respectively, for the mitochondrial cytochrome oxidase subunit 1 (COI) gene.

Performance of the 20-minute whole blood clotting test in detecting venom induced consumption coagulopathy from Russell's viper (Daboia russelii) bites.

The 20-minute whole blood clotting test (WBCT20) is used as a bedside diagnostic test for coagulopathic snake envenoming. We aimed to assess the performance of the WBCT20 in diagnosis of venom induced consumption coagulopathy (VICC) in Russell's viper envenoming. Adult patients admitted with suspected snake bites were recruited from two hospitals. WBCT20 and prothrombin time (PT) test were performed on admission. WBCT20 was done by trained clinical research assistants using 1 ml whole blood in a 5 ml borosilicate glass tube with a 10 mm internal diameter. The PT was measured by a semi-automated coagulation system and international normalised ratio (INR) calculated. VICC was defined as present if the INR was >1.4. The diagnostic utility of WBCT20 was determined by calculating the sensitivity and specificity of the WBCT20 on admission for detecting VICC. There were 987 snake bites where both WBCT20 and PT were done on admission samples. This included 79 patients (8 %) with VICC. The WBCT20 was positive in 65/79 patients with VICC (sensitivity 82 %; 95 % confidence interval [CI]: 72-90 %) and was falsely positive in 13/908 with no coagulopathy. The WBCT20 was negative in 895/908 snake bites with no coagulopathy (specificity: 98 % 95 % CI: 97-99 %) and was falsely negative in 14/79 with VICC. Using trained clinical staff, the WBCT20 test had a relatively good sensitivity for the detection of VICC, but still missed almost one fifth of cases where antivenom was potentially indicated.

Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell's Viper (Daboia russelii) Envenoming.

BACKGROUND: 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. METHODOLOGY AND FINDINGS: 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. CONCLUSION: 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.

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.

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.