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The hump-nosed pit viper (Genus: Hypnale) is a highly medically significant snake in Sri Lanka, responsible for the majority of venomous snakebites (22–77%). They are found throughout Sri Lanka and the Western Ghats region of India. The venom can lead to two types of effects: acute and long-term. Acutely, bites often result in local symptoms, with less common systemic effects such as acute kidney injury, venom-induced consumption coagulopathy, and thrombotic microangiopathy. We conducted a prospective observational study at Teaching Hospital Ratnapura, Sri Lanka, spanning six years, starting in June 2015. Patients bitten by hump-nosed pit vipers were followed up for two years, with assessments every three months to identify long-term effects. Data was gathered through interviewer-administered questionnaires. Out of 728 patients bitten by hump-nosed pit vipers, 22 (3%) were lost to follow-up. Forty-four (6.2%) experienced long-term effects, including chronic kidney disease (24; 3.4%), chronic wounds (five; 0.7%), amputations (five; 0.7%), fasciotomy-related wounds (four; 0.6%), and psychological illnesses (four; 0.6%). There were nine (1.3%) deaths in this group. Among those with chronic effects, 27 (61%) were males, and 17 (39%) were females, with ages ranging from 29 to 82 years (mean 57.6 years). The time it took to diagnose acute kidney injury from the snakebite was 18 h (interquartile range: 15–23.5 h), while the time to diagnose chronic kidney disease was 69 days (interquartile range: 64–74.75 days). In these patients, the estimated glomerular filtration rate was 29.3 mL/min/1.73 m2 (interquartile range: 14–50.75 mL/min/1.73 m2). Among the patients who did not develop long-term complications (662; 91%) 660 (90.7%) experienced local effects, and 82 (11.3%) developed systemic manifestations, including acute kidney injury in 60 (8%) and coagulopathy in 35 (5%). Following hump-nosed pit viper bites, a subset of patients may experience long-term health complications, including chronic kidney disease, chronic ulcers, amputations, fasciotomy-related wounds, and psychological illnesses, with chronic kidney disease being the most frequently observed among these manifestations. [ABSTRACT FROM AUTHOR]

Background: Hump-nosed vipers (HNV; Hypnale spp) are one of the medically important venomous snakes in Sri Lanka and South-Western regions of India. The haemostatic dysfunction due to HNV bites is poorly characterized by standard diagnostic tests performed to identify coagulopathy. We aimed to determine the usefulness of rotational thromboelastometry (ROTEM) parameters compared to 20-minute whole blood clotting test (WBCT20) and prothrombin time (PT) in understanding the coagulopathy of HNV bites. Methods: Twenty-three HNV snakebite patients in a prospective study of 127 consecutive snakebites were recruited. After recording details of the clinical presentation, PT/international normalized ratio (INR), WBCT20 and ROTEM delta were performed at presentation. Results: In this preliminary study, none of the patients had clinically apparent bleeding. Coagulopathy was detected by either WBCT20, INR or ROTEM in 13 HNV patients. Eleven had a coagulopathy detectable by ROTEM (either abnormal EXTEM-CT, INTEM-CT or FIBTEM-MCF) but with negative WBCT20. Of them, only two had prolonged INR values. Two patients had positive WBCT20 but with normal ROTEM and INR values. The remaining 10 patients did not show any coagulopathy either by INR, ROTEM or WBCT20. Conclusion: In this preliminary study with small number of sample size, ROTEM parameters appeared to be more sensitive to subtle changes in coagulation compared to WBCT20. The clinical utility of detecting these changes and their usefulness in managing snakebite should be explored further in a larger study. [ABSTRACT FROM AUTHOR]

Background: Bites by the hump-nosed pit vipers (HNPV) of the genus Hypnale are the commonest type of venomous snakebites in Sri Lanka. Their bites frequently cause local effects while rarely causing systemic envenoming, that may include acute kidney injury and coagulopathy. There are 3 species of genus Hypnale including H. hypnale, H. zara and H. nepa from which latter two are endemic to Sri Lanka. Virtually all studies on HNPV bites in Sri Lanka are focused on adults except two studies in paediatric group. The aims of this study were to describe the epidemiology and clinical manifestations of HNPV bites in a group of children admitted to a tertiary care hospital in Sri Lanka. Methodology/Principal findings: This was a prospective observational study carried out in Teaching Hospital Ratnapura, Sri Lanka over 27 months commencing from May 2020 including all children aged up to 14 years with the history of HNPV bites. There were 40 (55.6%) HNPV bites, of them 28 (70%) were males. The age was 84 months (50.2–120 months). Majority (n = 21;52.5%) were bitten during day-time (06:00–17:59) in home gardens (n = 20; 50%) on lower limbs (n = 24;60%). Most children (n = 30;75%) were admitted to the medical facility < 4 hour after the snakebite [90 min (40–210 min)] and the hospital stay was 4 days (3–5 days). Local envenoming was observed in 38 patients (95%) and systemic effects developed in 4 patients (10%) as mild coagulopathy. Local effects include local pain (n = 30; 94%), swelling (n = 38;95%), blistering (n = 11;27.5%), necrosis at the site of bite (n = 11; 27.5%), regional lymph node enlargement (n = 8;20%) and local bleeding (n = 4;10%). For the local effects, surgical interventions were needed in 10 children (25%) and 3 (7.5%) of them developed acute compartment syndrome leading to fasciotomy. Leucocytosis (n = 28;78%) and eosinophilia (n = 9;27%) were the prominent laboratory findings. All got recovered except in patients with fasciotomy who got permanent scar. Conclusions/Significance: Hump-nosed pit viper bites mostly cause local effects and rarely systemic envenoming in children. Compartment syndrome is common in children following their bites. Author summary: Snakebite is a neglected tropical disease affecting mostly rural communities who are engaging in agricultural activities. Many studies focus on adult snakebites and very few are describing on snakebites in paediatric group. Therefore, the understanding of epidemiological and clinical profile of snakebites in children is lacking and poorly characterized. In Sri Lanka, hump-nosed pit viper (Hypnale spp.) causes the commonest venomous snakebites because it inhabits all over the country and is found frequently in human habitat. We undertook a clinical study in Teaching Hospital Ratnapura in order to describe clinical and epidemiological characteristics of HNPV bites in children. There were 40 (56%) children with HNPV bites from which 95% (n = 38) developed local envenoming such as local pain, swelling, blistering and necrosis at the site of bite. Systemic envenoming was observed in 4 (10%) who had mild coagulopathy and 3 (7.5%) had non-specific envenoming features including abdominal pain and headache. The prominent finding was the occurrence of compartment syndrome in some children (n = 3;7.5%) who needed to open limb compartment (fasciotomy). [ABSTRACT FROM AUTHOR]

Hemipenial characteristics have historically provided a wealth of comparative morphological characters for the systematic classification of snakes. However, the organs remain poorly known in many groups, particularly tropical and burrowing lineages. Here, we report on hemipenial morphology for 12 species from five genera from the family Uropeltidae: Melanophidium punctatum, M. cf. wynaudense, Plectrurus perrotetii, Rhinophis karinthandani, R. melanoleucus, R. saffragamus, R. sanguineus, Teretrurus cf. hewstoni, Uropeltis bhupathyi, U. cf. ceylanica, U. macrolepis, and U. rajendrani. Many are photographed or illustrated here for the first time. In Melanophidium, the organ is bulbous and mushroomshaped, with the sulcus spermaticus winding through numerous convoluted folds. In Plectrurus and Teretrurus, it is simple, smooth, and conical. In Sri Lankan Rhinophis and some Uropeltis, the organ generally resembles previously described hemipenes from other species in those genera in being simple, subcylindrical, and covered in fine spines. However, a median lobular process is observed in the Indian species R. karinthandani, R. melanoleucus, and R. sanguineus, seemingly representing a novel bilobate morphology. One species, U. bhupathyi, exhibits a novel, bulbous morphology, but this may be an artifact of preservation. The hemipenes of the Uropeltidae and their sister group Cylindrophiidae resemble some typhlopoid blindsnakes more than their henophidian relatives such as pythons and boas. Whether this is due to convergence related to microhabitat, a form of sexual selection unrelated to ecomorphology, or symplesiomorphy from an ancestral snake morphology is unclear. Gross hemipenial morphology can now serve to diagnose uropeltids to the genus level or species group, though more data and comparative series are needed to determine whether other characters, such as the number and location of spines, can potentially differentiate taxa at finer scales. [ABSTRACT FROM AUTHOR]

Background: Hump-nosed pit viper is a medically important deadly venomous snake in Sri Lanka and is the commonest cause of venomous snakebites in the country. It frequently causes local effects and systemic manifestations such as acute kidney injury and coagulopathy that occur in less than 10% of all bites. This also includes some atypical presentations such as thrombotic microangiopathy and myocardial infarction. Currently, no antivenom is available for hump-nosed pit viper bites in Sri Lanka, and patients are managed with supportive treatment. This case illustrates an acute ischemic stroke following a hump-nosed viper bite, which is the second case in the literature.Case Presentation: A 71-year-old a Sinhalese male patient presented with left-sided hemiparesis with mouth deviation on day 2 of hump-nosed viper (Hypnale spp.) bite on the right foot. Non-contrast computed tomography of brain showed right ischemic stroke in internal capsule. He was given antiplatelets and statins and continued supportive treatment including limb physiotherapy and speech therapy. He recovered completely and was discharged on day 4 with clinic follow-up.Conclusions: Physicians should be aware that ischemic cerebral infarcts may occur following hump-nosed pit viper bites. [ABSTRACT FROM AUTHOR]

Envenoming by the hump-nosed pit viper (Hypnale hypnale) raises concern as it inflicts significant debilitation and death in the Western Ghats of India and in the adjacent island nation of Sri Lanka. In India, its medical significance was realized only during 2007 due to its misidentification as Echis carinatus and sometimes as Daboia russelii. Of late, several case reports have underlined the ineptness of the existing polyvalent anti-venom therapy against H. hypnale envenoming. Currently, H. hypnale bite has remained dreadful in India due to the lack of neutralizing anti-venom therapy. Hence, this study was undertaken to establish a systematic comparative, biochemical, pathological, and immunological properties of Sri Lankan H. hypnale venom alongside Indian E. carinatus, and D. russelii venoms. All three venoms differed markedly in the extent of biochemical activities including proteolytic, deoxyribonuclease, L-amino acid oxidase, 5'-nucleotidase, hyaluronidase, and indirect hemolytic activities. The venoms also differed markedly in their pathological properties such as edema, hemorrhage, myotoxic, cardiotoxic, and coagulant activities. The venoms showed stark differences in their protein banding pattern. Strikingly, the affinity-purified rabbit monovalent anti-venoms prepared against H. hypnale, E. carinatus, and D. russelii venoms readily reacted and neutralized the biochemical and pathological properties of their respective venoms, but they insignificantly cross-reacted with, and thus failed to show paraspecific neutralization of any of the effects of the other two venoms, demonstrating the large degree of variations between these venoms. Further, the Indian therapeutic polyvalent anti-venoms from VINS Bioproducts, and Bharath Serums and Vaccines failed to protect H. hypnale venom-induced lethal effects in mice. Author summary: In India, the 'Big four' snakes, viz. Naja naja, Bungarus cearuleus, Daboia russelii, and Echis carinatus are considered medically significant. Hence therapeutic polyvalent anti-venoms are prepared against the concoction of the venoms from said snakes. In India, the dreadful effects of Hypnale hypnale bite was realized only during 2007 due to its misidentification as Echis carinatus and or Daboia russelii bite. Several case reports from India and Sri Lanka have underscored the ineptness of Indian therapeutic anti-venoms against H. hypnale envenoming. As H. hypnale venom is not marketed in India, Sri Lankan H. hypnale venom was compared with Indian E. carinatus, and D. russelii venoms for their biochemical, pathological, and immunological properties. The venoms differed greatly in the said properties. The rabbit monovalent anti-venoms of H. hypnale, E. carinatus, and D. russelii venoms neutralized the activities of their respective venoms, but they insignificantly cross-reacted with, and failed to show paraspecific neutralization of the effects of the other two venoms. Further, the therapeutic polyvalent anti-venoms from VINS, and Bharat failed to neutralize the H. hypnale venom-induced lethal toxicity in mice. Thus, this study is pressing the need for suitable anti-venom to treat the dreadful H. hypnale bite in India. [ABSTRACT FROM AUTHOR]

Background: Hump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1–10%) following HNV envenoming. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites. Methods: We conducted a prospective cohort study of patients with confirmed HNV envenoming presenting to two large tertiary care hospitals in Sri Lanka. Demographics, bite details, clinical effects, complications and treatment data were collected prospectively. Blood and urine samples were collected from patients for coagulation and renal biomarker assays on admission, at 0-4h, 4-8h, 8-16h and 16-24h post-bite and daily until discharge. Follow-up samples were obtained 1 and 3 months post-discharge. Creatinine (sCr) and Cystatin C (sCysC) were measured in serum and kidney injury molecule-1 (uKIM-1), clusterin (uClu), albumin (uAlb), β2-microglobulin (uβ2M), cystatin C (uCysC), neutrophil gelatinase associated lipocalin (uNGAL), osteopontin (uOPN) and trefoil factor-3 (uTFF-3) were measured in urine. Definite HNV bites were based on serum venom specific enzyme immunoassay. Kidney Disease: Improving Global Outcomes (KDIGO) criteria were used to stage AKI. Two patients had chronic kidney disease at 3 month follow-up, both with pre-existing abnormal sCr, and one developed AKI following HNV envenoming. Results: There were 52 patients with confirmed HNV envenoming; median age 48y (Interquartile range [IQR]:40-59y) and 29 (56%) were male. Median time to admission was 1.87h (IQR:1–2.75h). Twelve patients (23%) developed AKI (AKI stage 1 = 7, AKI stage 2 = 1, AKI stage 3 = 4). Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, β2-microglobulin and clusterin, were elevated in patients who developed moderate/severe acute kidney injury. sCysC performed the best at 0–4 h post-bite in predicting moderate to severe AKI (AUC-ROC 0.95;95%CI:0.85–1.0) and no biomarker performed better than sCr at later time points. Conclusions: sCysC appears to be a better marker than sCr for early prediction of moderate to severe AKI following HNV envenoming. Author summary: Snakebite is a major public health problem associated with considerable morbidity and mortality worldwide. Acute kidney injury is one of the major systemic complications of snakebites. Its pathophysiology is poorly understood and the diagnosis is often delayed due to lack of sensitive biomarkers. We aimed to investigate the value of selected biomarkers in the early diagnosis of acute kidney injury following hump-nosed pit viper (Hypnale spp.) envenoming. In a group of 52 patients with confirmed hump-nosed pit viper envenoming acute kidney injury was found to be common and was associated with severe disease in some. Levels of five novel biomarkers, the functional marker serum Cystatin C and the damage markers urinary NGAL, cystatin C, β2-microglobulin and clusterin, were elevated in patients who developed moderate/ severe acute kidney injury. Serum Cystatin C performed better than serum creatinine in early prediction of moderate/severe acute kidney injury. Serum Cystatin C appears to be a promising novel biomarker in diagnosing acute kidney injury in the setting of hump-nosed pit viper envenoming. [ABSTRACT FROM AUTHOR]

Hump-nosed pit vipers of the genus Hypnale are highly venomous and reputed for the commonest venomous snakebites in Sri Lanka. They frequently cause local manifestations and less commonly cause systemic effects such as acute kidney injury and coagulopathy. There is no antivenom currently available in Sri Lanka for their envenoming. However, more and more complications of Hypnale bites are being recently described. Purpura fulminans, one of the rare complications of snakebites that we report following authentic Hypnale hypnale bite. A 58-year-old female was bitten by a hump-nosed viper and developed bilateral toe gangrenes, ultimately ended up with amputations. She got recovered with loss of toes in both feet for 46 days treatment at hospital. [Display omitted] • A rare case of describing purpura fulminans in snakebites. • First case of describing purpura fulminans in hump-nosed pit viper bites. • Patient recovered with loss of toes in both feet. • Thrombosis of dermal vessels is the predominant pathology. [ABSTRACT FROM AUTHOR]

Background Hump-nosed vipers of the genus Hypnale are the most common cause of venomous snakebites in Sri Lanka. The genus includes three species: Hypnale hypnale , Hypnale zara and Hypnale nepa. Of them, H. hypnale bites are the most common and are the subject of many publications. The epidemiology and clinical features of bites by the other two species have been less investigated. Methods We conducted a prospective observational study of H. zara bites from January 2015 to June 2020 at the Teaching Hospital, Ratnapura, Sri Lanka. Data were collected for 5.5 years in the wet zone of the island, where the principal investigator did assessment of all patients and the data collection. Results H. zara envenoming was confirmed through identification of dead or live snake specimens brought with the patients. Of the 480 patients with proven hump-nosed viper bites, H. zara bites accounted for 105 (22%), including dry bites (n=5 [5%]) and envenoming (n=100 [95%]), with gender distribution of 65 (62%) males and a mean age of 43.1 y. Most bites occurred on the lower limbs (n=71 [68%]) in the daytime (n=69 [66%]) in home gardens (n=45 [43%]). A total of 100 (95%) patients had local manifestations, including pain (n=100 [95%]), swelling (n=100 [95%]), bleeding (n=20 [19%]), bruising (n=11 [10%]), lymphadenopathy (n=10 [9%]), necrosis at the bite site (n=9 [9%]) and blistering (n=8 [8%]). Seven (6.7%) patients showed systemic effects, including acute kidney injury (n=2 [2%]), microangiopathic haemolysis (n=2 [2%]), sinus bradycardia (2 [2%]) and one (1%) each had coagulopathy, thrombotic microangiopathy, Kounis syndrome and ischaemic changes on electrocardiography. Eosinophilia was a significant haematological finding (n=26 [25%]) and 16 (15%) had leucocytosis and 15 (14%) had neutrophilia. Ninety six percent of patients (n=101) recovered. Antivenom is not available for hump-nosed viper bites in Sri Lanka and therefore patients were managed conservatively. Conclusions This study shows that H. zara bites mainly cause local envenoming and rarely systemic effects. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is the most serious clinical manifestation of the Sri Lankan hump-nosed pit viper (Hypnale spp.) bites. Thrombotic microangiopathy (TMA) is increasingly recognized in association with AKI in cases of Hypnale spp envenomation. We investigated AKI in a cohort of cases of Hypnale envenomation, its association with TMA and the early diagnostic value of common biomarkers for AKI occurring. We conducted a prospective observational study of suspected viper bites and included 103 confirmed cases of Hypnale envenomation, based on venom specific enzyme immunoassay of blood. AKI was defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Thrombotic microangiopathy was diagnosed based on thrombocytopenia (platelet count < 150,000 × 103/μL) and microangiopathic haemolytic anaemia (MAHA). We investigated the diagnostic performance of creatinine, platelet count and INR for AKI within 4 h and 8 h post-bite by area under the receiver operator characteristic curve (AUC–ROC). Ten patients developed AKI: seven AKI stage 1 and three AKI stage 3. Ten patients (10%) developed thrombocytopaenia while 11 (11%) had MAHA. All three AKI stage 3 had thrombocytopaenia and MAHA fulfilling the criteria for TMA. Two of them presented with oliguria/anuria and all three required haemodialysis. Serum creatinine within 4 h post-bite was the best predictor of AKI with AUC-ROC of 0.83 (95% CI: 0.67–0.99) and was no better within 8 h of the bite. We found that AKI is uncommon in Hypnale spp. envenomation, but an important serious complication. Severe AKI was associated with TMA. A creatinine within 4 h post-bite was the best predictor of AKI. [ABSTRACT FROM AUTHOR]

Hypnale hypnale, Hypnale zara and Hypnale nepa are the three species of Hump nosed pit vipers that are implicated in human bites in Sri Lanka. H. zara and H. nepa are two endemic species to the country. The objective of the study was to characterize epidemiology and clinical features after different Hump nosed pit viper species bites. A prospective observational study was conducted in Base Hospital Deniyaya from 2013 to 2015. Hump nosed pit viper as the offending snake was identified when the victims brought live or dead specimens. Species identification of dead specimen was done by a herpetologist. Clinical details were recorded during the hospital stay. 83 Hump nosed pit viper bite patients (19–81 years) were studied. Fifty two dead specimens were identified as 39 of H. zara and 13 of H. hypnale by the herpetologist. No H. nepa was identified. Thirty one live snakes were identified as Hump nosed pit vipers and released in to the wild. Envenoming was reported throughout the year. Eighty (96.4%) were daytime bites. Hands (43.4%), feet (55.4%) and arms (1.2%) were affected sites. Sixty two (74.7%) were bitten in tea plantations. All had pain over bite site. Overall, sixty nine (83.1%) had local swelling, seven (8.4%) extensive limb swelling, nineteen (22.9%) haemorrhagic blisters, and seven (8.4%) regional lymphadenopathy. Four (4.8%) patients had incoagulable blood by 20WBCT. H. zara bites had 28.2% haemorrhagic blisters, 7.7% extensive limb swelling and 2.6% coagulopathy. H. hypnale bites had 7.7% each extensive limb swelling and coagulopathy and 23.1% haemorrhagic blisters. None developed elevated serum creatinine. Neurotoxicity was not noted. Hump nosed pit viper bites caused substantial morbidity. Risk factors included day time outdoor activities and occupation. Pain, extensive limb swelling, bite site swelling, haemorrhagic blisters, regional lymphadenopathy and coagulopathy were prominent clinical features. Nephrotoxicity and neurotoxicity were notably absent. Clinical features varied depending on the species implicated. • 74.7% were bitten by Hump-nosed vipers while they were working in Tea lands. • Pain, swelling, haemorrhagic blisters, lymphadenopathy and coagulopathy were common. • Severe systemic envenoming was not noted. [ABSTRACT FROM AUTHOR]

Green pit viper (Trimeresurus trigonocephalus) is endemic to Sri Lanka and bites are reported from tropical rain forest and plantation areas. As scant data exists on clinico-epidemiological features of Sri Lankan green pit viper bite, objective of this study was to address this knowledge gap. A prospective observational study was conducted in Base Hospital Deniyaya from October 2013 to September 2015. Green pit viper as the offending snake was identified when the victims brought live or dead specimens. When the specimen was not available, green pit viper was identified by the victim pointing to preserved specimens and photographs of green pit viper and different similar appearing snakes. Clinical details were recorded during the hospital stay. Twenty four green pit viper bite patients (17–68 years) were studied. All cases were daytime bites despite green pit viper being a nocturnally active snake. Sixteen patients (67%) were bitten while they were working in tea plantation. Hands (42%), feet, (33%), forearms (8%), legs (8%), thighs (4%) and shoulders (4%) were the sites of bites. Thirteen (54%) had extensive limb swelling. Nine (38%) had local swelling and two had no swelling. Three (12.5%) developed haemorrhagic blisters. Four (17%) had regional lymphadenopathy. Two (8%) developed non clotting blood by the TWBCT. Green pit viper bites caused substantial morbidity. Risk factors included day time outdoor activities in bordering villages of tropical rain forests and occupation. Pain, extensive limb swelling and bite site swelling were prominent clinical features. However haemorrhagic blisters, regional lymphadenopathy and coagulopathy were reported. Nephrotoxicity and neurotoxicity were notably absent. • One third of study group were bitten by Sri Lankan Green Pit Viper while they were working in tea plantation • As hand was the commonest bite site (41.6%), wearing gloves could be useful to prevent envenoming • Though extensive limb swelling and elevated 20WBCT were reported, severe systemic envenoming was not noted [ABSTRACT FROM AUTHOR]

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. Image 1 • The nephrotoxic effect of the venom of Hypnale hypnale from Sri Lanka was investigated. • Venom induced several functional alterations in the isolated rat perfused kidney. • Venom was cytotoxic for proximal and distal renal epithelial cells in culture. • This experimental model of nephrotoxicity agrees with clinical observations. [ABSTRACT FROM AUTHOR]

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. Highlights • A patient envenomed by Hypnale hypnale developed coagulopathy. • In absence of antivenom, coagulopathy was treated with fresh frozen plasma (FFP). • FFP was continued to be consumed without reversal of the coagulopathy. • FFP in absence of antivenom needs high quality clinical evidence. [ABSTRACT FROM AUTHOR]

Envenomations by hump-nosed pit vipers (HNVs) are frequent in Sri Lanka and in South India. Until recently, HNV was considered a moderately venomous snake. Here, we report a case of a previously healthy female developing all the known serious complications, plus some previously unreported complications following a HNV envenomation. She had muscarinic symptoms like profuse sweating and salivation within a couple of minutes and a seizure several minutes after envenomation. Her acute kidney injury (AKI) was swift onset and progressed to end-stage renal failure at three months. She had mild parotid swelling, crepitations in her lungs, and edema of the bitten leg. She had evidence of microangiopathic hemolytic anemia and hemolytic uremic syndrome as well. She developed local tissue necrosis, a non-ST-elevation myocardial infarction (non-STEMI), and anterior ischemic optic neuropathy (AION) following the envenomation. We believe the best explanation for her swift onset complication is intravascular injection of venom. We believe ischemia due to thrombotic microangiopathy has contributed to local tissue necrosis. Those ischemia and kidney failure have contributed to non-STEMI and AION. We illustrate the issue of the sluggish progress made by medicine in understanding the complications of envenomation by using HNV as an example. [ABSTRACT FROM AUTHOR]

Background Hump-nosed pit vipers (Hypnale hypnale) are highly venomous snakes found in Sri Lanka and the Western Ghats region of India. They are the most common cause of venomous snakebites in Sri Lanka, mainly causing local envenoming leading to pain, swelling and necrosis. Systemic envenoming causing acute kidney injury and coagulopathy are more commonly recognized following their bites. Method A series of 465 patients with hump-nosed viper bites was prospectively studied over four years from January 2014. All patients were assessed and the data were collected by the principal investigator (primary data). Results Forty-four (9.5%) patients developed acute kidney injury, of which 23 (5%) were proven cases and 21 (4.5%) were probable cases. Of the proven cases, 4 (17%) progressed to chronic kidney disease and 12 (52%) had thrombotic microangiopathy, from which 11 (48%) developed haemolytic uremic syndrome and 1 (4%) had thrombotic thrombocytopenic purpura. Twelve (52%) showed microangiopathic haemolysis and 15 (65%) had thrombocytopenia. Oliguria was observed in 10 (43%) whereas 7 (30%) each had anuria and normal urine output. Ten patients (43%) developed haematuria, from which 6 had microscopic haematuria and 4 had macroscopic haematuria. Proteinuria was observed in 8 (35%). Coagulopathy developed in 3 (13%) patients. In probable cases, 3 (14%) died due to complications of kidney injury. Conclusion A significant proportion of patients develop acute kidney injury following hump-nosed pit viper bite. Who will develop acute kidney injury or succumb to the venom is unpredictable. Reliable and accessible treatments are a critical unmet need. [ABSTRACT FROM AUTHOR]

Sri Lanka homes 3 species of hump-nosed pit vipers including Hypnale Hypnale , H. zara and H. nepa from which, latter 2 are endemic to the country. Even though former 2 are the subject of several publications, no major clinical studies have been done regarding H. nepa bites. As these snakes confine only to central hills of the country, their bites are very rare. The objectives of this study were to describe epidemiological and clinical features of H. nepa bites. A prospective observational study was conducted for patients admitted with H. nepa bites to Teaching Hospital, Ratnapura, Sri Lanka for 5 years commencing from June 2015. Species identification was done using a standard key. There were 14 (3.6%) patients with H. nepa bites of which 9 (64%) were males and 5 (36%) were females. Their age ranged from 20 to 73 years (median 37.5). Seven bites (50%) occurred on lower limbs. Majority of bites (10; 71%) happened at daytime [0600–1759 h] in tea estates (8; 57%). Most patients (8; 57%) were admitted within 1–3 h from bite. Hospital stay was 2.5 days (IQR 2–3). Local envenoming was observed in all patients including local pain and swelling [mild (7; 50%), moderate (5; 36%), severe (2; 14%)], local bleeding (1; 7%) and lymphadenopathy (1; 7%). Nonspecific features were observed in 3 (21%). Systemic manifestations were found in 2 (14%) including microangiopathic haemolytic anaemia and sinus bradycardia. Two (14%) had myalgia. H. nepa bites frequently cause local envenoming. But, rarely systemic manifestations may occur. [Display omitted] • Clinico-epidemiology of H. nepa bites is described. • H. nepa is an endemic species in Sri Lanka. • No antivenom is currently available for these bites. • They frequently cause local effects and rarely systemic manifestations. [ABSTRACT FROM AUTHOR]

Green pit viper is a venomous endemic snake in Sri Lanka. But little is known regarding its envenoming in the country. This study was carried out in order to find out epidemiology and clinical profile of its bites. A series of 17 patients with Sri Lankan Green pit viper ( Trimeresurus trigonocephalus ) bites was prospectively studied over 4 years. The mean age was 36 ½ years (range 12–61 years) and comprised 14 (82%) males. Except one case, all bites occurred during day time (0600 h-1800 h) due to inadvertent provocation. In 13 cases (76%) bite took place in estates (tea or cinnamon) and 8 patients (47%) were estate workers. The bitten sites were upper limbs in 11 cases (65%) and lower limbs in 6 cases (35%). Ten patients (59%) brought the offending snake to the hospital and one patient was asymptomatic. Sixteen (94%) developed local envenoming features- 16 (94%) local pain and swelling, 6 (35%) local bleeding and lymphadenopathy and blistering in 4 (24%) patients. Systemic envenoming developed in 4 (24%) patients including 3 (18%) with coagulopathy that was treated with fresh frozen plasma. One (6%) patient developed bradycardia. Sri Lankan Green pit viper bites commonly occurs in estates and causes local envenoming frequently and coagulopathy occasionally. [ABSTRACT FROM AUTHOR]

A 74-year-old previously healthy woman was bitten by a hump-nosed pit viper ( Hypnale hypnale ) at dusk causing incoagulable blood lasting for 6 days. Further, she developed ecchymoses over her forearms, upper arms, hands, and lower back on day 4 after the snakebite, and microangiopathic hemolytic anemia (MAHA). Features of this nature are rare after hump-nosed pit viper bite. [ABSTRACT FROM AUTHOR]

Trimeresurus trigonocephalus (Sri Lankan Green pit viper) is a moderately venomous arboreal snake endemic to Sri Lanka. Even though, its bites are not uncommon, published reports of such cases are limited to three in literature. We report three cases of coagulopathy following Green pit viper bites and treatment with fresh frozen plasma. [ABSTRACT FROM AUTHOR]

Abstract: The knowledge of venom pharmacokinetics is essential to improve the understanding of envenomation pathophysiology. Using a double-sandwich ELISA, this study investigated the pharmacokinetics of the venom of hump-nosed pit viper (Hypnale hypnale) following intravenous and intramuscular injections into rabbits. The pharmacokinetics of the venom injected intravenously fitted a three-compartment model. There is a rapid (t 1/2π = 0.4 h) and a slow (t 1/2α = 0.8 h) distribution phase, followed by a long elimination phase (t 1/2β = 19.3 h) with a systemic clearance of 6.8 mL h−1 kg−1, consistent with the prolonged abnormal hemostasis reported in H. hypnale envenomation. On intramuscular route, multiple peak concentrations observed in the beginning implied a more complex venom absorption and/or distribution pattern. The terminal half-life, volume of distribution by area and systemic clearance of the venom injected intramuscularly were nevertheless not significantly different (p > 0.05) from that of the venom injected intravenously. The intramuscular bioavailability was exceptionally low (F i.m. = 4%), accountable for the highly varied median lethal doses between intravenous and intramuscular envenomations in animals. The findings indicate that the intramuscular route of administration does not significantly alter the pharmacokinetics of H. hypnale venom although it significantly reduces the systemic bioavailability of the venom. [Copyright &y& Elsevier]

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. [Copyright &y& Elsevier]

Hump-nosed pit vipers (Genus Hypnale) are venomous snakes from South India and Sri Lanka. Envenoming by Hypnale species may cause significant morbidity and is characterized by local envenoming and less commonly coagulopathy and acute renal failure. Currently there are three nominal species of this genus: H. hypnale, H. zara and H. nepa. This study investigates the biochemical and pharmacological properties of the venoms from the three Hypnale species in Sri Lanka. The three Hypnale venoms had similar chromatographic profiles using reverse phase high performance liquid chromatography and fractions with procoagulant activity were identified. Hypnale venoms had potent cytotoxicity in cultured rat aorta smooth muscle cells with similar IC50 values. The venoms had weak neurotoxic and myotoxic activity in the isolated chick biventer muscle preparation. They had mild procoagulant activity with close MCC5 values and also phospholipase activity. Locally available polyvalent antivenom did not neutralise any venom effects. The study demonstrates that the three Hypnale venoms are similar and cytotoxicity appears to be the most potent effect, although they have mild procoagulant activity. These findings are consistent with clinical reports. [ABSTRACT FROM AUTHOR]

Abstract: Snakebite is a major medical problem in developing Asia. Hump-nosed pit viper (Genus Hypnale) causes the most number of snakebites with significant morbidity and mortality in Sri Lanka. Even though there are three species (Hypnale hypnale, Hypnale zara and Hypnale nepa) in Sri Lanka there are few published literature on species-specific clinico-epidemiological data. This report describes an authenticated fatal case of a 47 years old male due to coagulopthy and acute kidney injury following envenoming by H. zara in Sri Lanka. [Copyright &y& Elsevier]