Evaluation of the Inhibitory Potential of Synthetic Peptides Homologous to CDR3 Regions of a Monoclonal Antibody against Bothropic Venom Serine Proteases.

Snakebite accidents, neglected tropical diseases per the WHO, pose a significant public health threat due to their severity and frequency. Envenomation by Bothrops genus snakes leads to severe manifestations due to proteolytic enzymes. While the antibothropic serum produced by the Butantan Institute saves lives, its efficacy is limited as it fails to neutralize certain serine proteases. Hence, developing new-generation antivenoms, like monoclonal antibodies, is crucial. This study aimed to explore the inhibitory potential of synthetic peptides homologous to the CDR3 regions of a monoclonal antibody targeting a snake venom thrombin-like enzyme (SVTLE) from B. atrox venom. Five synthetic peptides were studied, all stable against hydrolysis by venoms and serine proteases. Impressively, four peptides demonstrated uncompetitive SVTLE inhibition, with Ki values ranging from 10-6 to 10-7 M. These findings underscore the potential of short peptides homologous to CDR3 regions in blocking snake venom toxins, suggesting their promise as the basis for new-generation antivenoms. Thus, this study offers potential advancements in combatting snakebites, addressing a critical public health challenge in tropical and subtropical regions.

Comparing cost of F(.ab')2AV vs FabAV in the treatment of copperhead envenomation-One center's experience.

The definitive treatment of North American crotalid snakebites is antivenin. In 2000, an FabAV antivenom (CroFab®) was introduced and in 2022, F(ab')2AV (Anavip®) was approved for treatment of copperhead bites. Our center that sees primarily copperhead snake bites added the recently approved treatment as a second option for the 2022 snake bite season. This brief report we describe our initial experience with the two antivenins via retrospective chart review: the cost, charge, laboratory differences, response to therapy, complications and duration of hospitalization of admitted patients with copperhead envenomation. Using three independent reviewers in this IRB exempt report we found 31 patients with copperhead bites (7 exclusions) leaving 19 adults and 7 children for analysis. We found there was no difference in age, sex, presence of lab abnormalities, total vials administered, or length of stay. There was significant differences in hospital costs and charges to the patient. Future research should include multi-center experiences comparing the two antivenins.

Compliance with national snakebite treatment guidelines in rural Sri Lankan hospitals: a cluster randomized controlled trial of a brief educational intervention.

BACKGROUND: Snakebite is a global health problem that predominantly occurs in rural areas. In Sri Lanka, the majority of snakebite patients first present to smaller rural primary hospitals. Improving care delivered at rural hospitals has the potential to reduce morbidity and mortality from snakebites. OBJECTIVE: In this study, we evaluated whether an educational intervention would increase compliance with national snakebite treatment guidelines in primary hospitals. METHODS: The hospitals were randomized into educational intervention (n = 24) and control groups (n = 20). The intervention hospitals received a brief educational intervention based on Sri Lankan Medical Association (SLMA) guidelines on the management of snakebites. Control hospitals had free access to the guidelines but no additional promotion. Four outcomes were assessed: pre- and post-test knowledge at the completion of a one-day workshop of educational intervention (intervention group only); improvement in the quality of the patient's medical records; appropriateness of transfers to higher hospitals; and quality of overall management graded by a blinded expert. The data was collected over a period of 12 months. RESULTS: All case notes of snakebite hospital admissions were reviewed. There were 1021 cases in the intervention group hospitals and 1165 cases in the control hospitals. Four hospitals in the intervention group and three hospitals in the control group did not have snakebite admissions and were excluded from the cluster analysis. The absolute quality of care was high in both groups. Post-test knowledge was improved (p < 0.0001) following the intervention group's educational workshop. There was no statistical difference between the two groups in terms of clinical data documentation in hospital notes (scores, p = 0.58) or transfer appropriateness (p = 0.68)-both of which were significantly different from the guidelines. CONCLUSION: Education of primary hospital staff improved the immediate knowledge gained but did not improve record-keeping or the appropriateness of inter-hospital patient transfer. TRIAL REGISTRATION: The study was registered with Sri Lanka Medical Associations' clinical trial registry. Reg. No SLCTR -2013-023. Registered: 30/07/2013.

Venomous animals in a changing world.

The climatic changes of the next decades will modify human and livestock interactions with venomous animals; Some venomous species will disappear in the coming decades; Other venomous species will shift their distributions or increase their geographic ranges invading new countries that may not have specific antivenoms.

Effectiveness of clotting factor replacement therapy after antivenom treatment on coagulopathic envenomation following green pit viper bites: a retrospective observational study.

BACKGROUND: Green pit vipers (GPVs), namely Trimeresurus albolabris and Trimeresurus stejnegeri accounts for most snakebites in Southern China. Green pit viper venom contains thrombin-like enzymes, resulting in defibrination syndrome. Using of clotting factor replacement after antivenom administration is controversial. The objective of this study was to investigate the effects of clotting factor replacement in coagulopathic patients with T. albolabris and T. stejnegeri bites after antivenom administration. METHODS: We retrospectively reviewed 123 patients who were bitten by T. albolabris and T. stejnegeri and were admitted to the Emergency Department of a hospital in Guangzhou, Southern China, from 2013 to 2019. Recovery of prothrombin time (PT) and fibrinogen level were compared among (1) fresh-frozen plasma (FFP) group; (2) cryoprecipitate (cryo) group; (3) FFP and cryo group; and (4) control group after antivenom administration. RESULTS: The incidence of coagulopathy was 31%. Persistent and late coagulopathy were the most common patterns among four groups. The median reduction in PT was 20.1 ± 31.2 s for FFP and cryo group. The median increase in fibrinogen level was very small: 0.05 ± 0.20 g/L for FFP group, 0.09 ± 0.37 g/L for cryo group and 0.07 ± 0.31 g/L for FFP and cryo group, respectively. The percentage of unimproved PT was markedly higher in the FFP and cryo group than the control group (P = 0.01 by log-rank test, P = 0.02 by Gehan-Breslow-Wilcoxon test). The percentage of unimproved fibrinogen level tended to be worse in the FFP and cryo group than the control group, but the different was marginal (P = 0.05 by Gehan-Breslow-Wilcoxon test, P = 0.07 by log-rank test). A total of 7.8% (7/90) of the patients in the clotting factor replacement groups developed anaphylaxis and heart failure. CONCLUSION: There is no improvement in coagulopathy profile in patients with T. albolabris and T. stejnegeri bites who received clotting factor replacement after antivenom administration. But the results from GPVs may not be generalized to other species of venomous snakes.

Isolated Ptosis Following a Vipera aspis Bite.

In Spain, snakebites are uncommon medical emergencies that cause barely 100 hospitalizations annually. Most of the venomous bites are by snakes of the Viperidae family. Venom from Vipera snakes is reported to have cytotoxic and hematotoxic effects, and neurological effects have also been described. Ptosis (cranial nerve III palsy) is the most common sign, although any cranial nerve can be affected. We describe isolated ptosis, which was very likely after a Vipera aspis bite in the East Catalonian Pyrenees. No antivenom was administered. The ptosis resolved spontaneously within 10 h. Although neurologic findings are usually mild, they indicate a moderate or severe envenomation. Treating snakebites can be challenging for clinicians, especially when there are uncommon clinical manifestations. A toxicologist at a poison center should be consulted to help guide management. Development of local protocols may provide clinical support.

Therapeutic Plasma Exchange for Venom-Induced Thrombotic Microangiopathy Following Hump-Nosed Pit Viper (Genus: Hypnale) Bites: A Prospective Observational Study.

INTRODUCTION: -Thrombotic microangiopathy (TMA), which is the triad of acute kidney injury (AKI), microangiopathic hemolytic anemia (MAHA), and thrombocytopenia, is a rare complication of snakebites, and in Sri Lanka, it is commonly seen with hump-nosed pit viper (HNPV) bites. METHODS: -We conducted a prospective observational study of patients with AKI caused by HNPV bites in Teaching Hospital, Ratnapura, Sri Lanka for 6 y, commencing in June 2015. Some patients with TMA underwent therapeutic plasma exchange (TPE) and some did not. These 2 groups were compared. Statistical analysis was carried out using Minitab 18.1. Data were presented as median (IQR). RESULTS: -There were 52 (8%) patients with TMA, of whom 21 (45%) were in the TPE group and 26 (55%) were in the non-TPE group. TPE improved time to platelet correction (4 d [IQR, 4-5 d] vs 7 d [IQR, 5-9 d]; P=0.009), time to MAHA correction (5 d [IQR, 3-4 d] vs 7 d [IQR, 6-9 d]; P=0.004), time to prothrombin time (PT)/international normalized ratio (INR) correction (1 d [IQR, 1-2 d] vs 3 d [IQR, 3-4 d]; P=0.003), and time to 20 min whole blood clotting test (WBCT20) correction (2 d [IQR, 1-2 d] vs 3 d [1QR 2-3 d]; P=0.020). Renal recovery was predicted by TPE (P=0.048) and highest creatinine level (P=0.001). There was no association between TPE and dialysis dependency at discharge (P=0.597), length of hospital stay (P=0.220), and the number of dialysis cycles prior to discharge (P=0.540). TPE did not improve the number of blood transfusions (5 packs [IQR, 3-8.5 packs] vs 4 packs [IQR, 0-9 packs]; P=0.290). CONCLUSIONS: -TPE is effective for TMA in the early correction of platelet counts, MAHA, PT/INR, and WBCT20 in HNPV bites.

Kounis Syndrome Following Hypnale zara (Hump-Nosed Pit Viper) Bite in Sri Lanka.

A 47-y-old man was bitten by a hump-nosed viper (Hypnale zara) and gradually developed retrosternal chest pain associated with ST segment elevation on electrocardiogram. He had normal troponin I levels and no evidence of coagulopathy. Initially, he was managed as having anterior ST elevation myocardial infarction with thrombolysis. Later, because troponin levels were normal, he was suggested to have the type I variant of Kounis syndrome (allergic coronary artery spasm). This was supported by high eosinophil counts in peripheral blood. He was successfully managed with supportive treatment and discharged 6 d after the snakebite. Cardiac complications are rarely reported after hump-nosed viper bites, and clinical reports of coronary vasospasm after snakebites are extremely rare in the literature. This is the first known report of Kounis syndrome after a hump-nosed viper bite.

Comparative study of the in vivo toxicity and pathophysiology of envenomation by three medically important Egyptian snake venoms.

Snakebite envenomation is a serious medical problem in many developing tropical and subtropical countries. Envenomation is registered by the World Health Organization as a neglected tropical disease due to critical shortages in the production of antivenom. Envenomation causes more than 100,000 deaths annually. Snakebites result in several effects to include edema, blistering, hemorrhage, necrosis and respiratory paralysis. Antivenom is the preferred treatment for the systemic effects of snakebite envenomation, though these are often ineffective in neutralizing venom toxin-induced local tissue damage. To effectively treat snakebites, it is important to determine the lethal potency and pathophysiological effects induced by specific snake venoms. In the current study, we compared the lethality, and the hemorrhagic and dermonecrotic activities of venoms from three snakes in Egypt that are the primary causes of local tissue necrosis. Our data show that the intraperitoneal median lethal doses (LD50) for Cerastes cerastes, Echis carinatus and Naja nigricollis venoms are 0.946, 1.744 and 0.341 mg/kg mouse body weight, respectively. These results indicated that N. nigricollis venom is the most toxic and significantly accelerated the time of death compared to the other two venoms. However, no hematoma or associated edema appeared upon sub-plantar injection of N. nigricollis venom into the mice hind paw. Two hours following intradermal injection of C. cerastes and E. carinatus venoms, macroscopic analysis of the inner surface of mouse skin showed severe hemorrhagic lesions, whereas only insignificant hemorrhagic lesion appeared in mice injected with the highest dose of N. nigricollis venom. Furthermore, the minimum necrotic doses (MND) for the same venoms were 43.15, and 70.87 µg/mouse, or not observed in the case of N. nigricollis venom, respectively. These LD50 values and pathophysiological results can be used to guide development of antivenom against bites by these dangerous Egyptian snakes.

An Appraisal of Antidotes' Effectiveness: Evidence of the Use of Phyto-Antidotes and Biotechnological Advancements.

Poisoning is the greatest source of avoidable death in the world and can result from industrial exhausts, incessant bush burning, drug overdose, accidental toxication or snake envenomation. Since the advent of Albert Calmette's cobra venom antidote, efforts have been geared towards antidotes development for various poisons to date. While there are resources and facilities to tackle poisoning in urban areas, rural areas and developing countries are challenged with poisoning management due to either the absence of or inadequate facilities and this has paved the way for phyto-antidotes, some of which have been scientifically validated. This review presents the scope of antidotes' effectiveness in different experimental models and biotechnological advancements in antidote research for future applications. While pockets of evidence of the effectiveness of antidotes exist in vitro and in vivo with ample biotechnological developments, the utilization of analytic assays on existing and newly developed antidotes that have surpassed the proof of concept stage, as well as the inclusion of antidote's short and long-term risk assessment report, will help in providing the required scientific evidence(s) prior to regulatory authorities' approval.

Venom-Induced Consumption Coagulopathy Following Hump-Nosed Pit Viper (Genus: Hypnale) Envenoming in Sri Lanka: Uncertain Efficacy of Fresh Frozen Plasma.

INTRODUCTION: Hump-nosed pit vipers (Hypnale spp) cause the highest number of venomous snakebites in Sri Lanka. Bites commonly cause local envenoming leading to local pain, swelling, and necrosis of the site of the bite. Acute kidney injury is the most common systemic manifestation, and some patients develop venom-induced consumption coagulopathy (VICC). Genus Hypnale comprises 3 species. Of them, H hypnale is found in Sri Lanka and the Western Ghats region of India. The other 2 (H nepa and H zara) are endemic species in Sri Lanka. METHODS: This study included 500 patients with hump-nosed viper bites studied prospectively over 4.5 y starting June 2014. All patients were assessed and the data were collected by the principal investigator (primary data). A subgroup of patients who developed VICC is described. There were 2 groups, including proven (patients with the specimen of the snake) and probable (specimen of snake not available) bites. RESULTS: Thirty (n=500; 6%) patients developed VICC; of them, 17 (3%) were proven cases, and 13 (2%) were probable cases. In both groups, 24 (80%) recovered, 2 (7%) progressed to chronic kidney disease, 1 (3%) died of severe hemostatic dysfunction, and 3 (10%) were lost to follow-up. Systemic bleeding was observed in 16 patients (53%), including hematuria (microscopic and gross) in 8 (27%) and venipuncture bleeding in 5 (17%). Eleven (37%) developed local bleeding at the site of the bite. Fresh frozen plasma was administered to 20 patients (67%), among whom only 11 (55%) experienced early correction of VICC. In both groups, 15 (50%) developed acute kidney injury, and 2 (7%) progressed to chronic kidney disease. Microangiopathic hemolysis was observed in 18 patients (60%) and thrombocytopenia in 16 (53%). Thrombotic microangiopathy was detected in 13 patients (43%), of whom 10 (33%) developed hemolytic uremic syndrome and 2 (7%) had thrombotic thrombocytopenic purpura. Of patients with VICC in the proven group, 94% (n=16) was caused by H hypnale and 1 (6%) was caused by H zara. In the proven group, median international normalized ratio was 3.7 (interquartile range 1.6-5.0); in the probable group, it was 5.0 (interquartile range 2.1-5.4). CONCLUSIONS: We found that 6% of patients develop hemostatic dysfunction after hump-nosed viper bites. However, which patients will develop coagulopathy or die of envenoming is unpredictable. Reliable and accessible treatments are unmet essential needs because antivenoms for these bites are currently not available in the country. Therapy with fresh frozen plasma has doubtful efficacy in early correction of VICC and needs further evaluation.

Thrombotic Microangiopathy Following Hypnale zara (Hump-Nosed Pit Viper) Envenoming: The First Known Case Report from Sri Lanka.

A 65-y-old previously healthy farmer developed thrombotic microangiopathy (TMA) comprising the triad of acute kidney injury, microangiopathic haemolysis, and thrombocytopenia after a proven Hypnale zara (hump-nosed pit viper) bite. He developed coagulopathy, which was treated with fresh frozen plasma, and underwent 8 cycles of hemodialysis. He is being followed up in the nephrology clinic for acute kidney injury. TMA caused by Hypnale hypnale, the commonest species of genus Hypnale, has previously been reported, but this is the first known case of TMA following a bite by H zara, the endemic species in Sri Lanka.

High snakebite underreporting rate in the Centre Region of Cameroon: an observational study.

BACKGROUND: In Cameroon, since the first epidemiological week held in 2015, snakebites have been registered among Potential Epidemic Diseases (PED). In the Centre Region, the most densely populated of the country, weekly reports of snakebites are generated at health districts level for monthly data updates. METHODS: To contribute to the better management of snakebite cases, an observational study was conducted to assess the snakebite reporting rate in the Centre Region of Cameroon. The results of this retro-prospective survey were confronted to those of the weekly epidemiological surveillance system, recorded in the PED regional data base. RESULTS: The incidence of bites was relatively high (36.6 bites per 100,000 inhabitants), as well as the general attack rate (about 49 envenomations per 100 victims). The lethality recorded was 2.5% and the mortality was about 1 death per 100,000 inhabitants a year. The sex ratio was largely female biased (61.6%). The bites occurred mostly during the rainy season (73.0%). Bitten victims were mainly farmers (47.4%), and agriculture was the main risk factor. The comparative analysis of the data suggested a high non-reporting rate of snakebite cases (67.8%). CONCLUSION: Snakebite is an endemic condition in the Centre Region of Cameroon. Because of the high rate of non-reporting of cases, the collection of information from the registers of the health facilities only appears not enough to assess the real importance of envenomation in this Region.

Thrombotic Microangiopathy, Hemolytic Uremic Syndrome, and Thrombotic Thrombocytopenic Purpura Following Hump-nosed Pit Viper (Genus: Hypnale) Envenoming in Sri Lanka.

Thrombotic microangiopathy (TMA), which includes the spectrum of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, is an uncommon complication of hump-nosed pit viper envenomation. We describe 4 cases of TMA following hump-nosed pit viper (Hypnale spp) bites in Sri Lanka. The first case is a typical TMA that spontaneously resolved with supportive treatments. The second and third cases are related to hemolytic uremic syndrome complicated with acute kidney injury that required hemodialysis. The fourth case is thrombotic thrombocytopenic purpura associated with acute kidney injury that required hemodialysis and therapeutic plasma exchange. For each patient we describe the circumstances of the bite, clinical features, laboratory findings, and management.

The Association Between Heat Waves and Other Meteorological Parameters and Snakebites: Israel National Study.

BACKGROUND: Published annual estimates report a global burden of 2.5 million snakebite cases and >100,000 deaths. In Israel, envenomations are the third most frequent cause of poisonings that are of moderate to major clinical severity. Most studies focus on the clinical descriptions of snakebites in tropical climates, and we sought to investigate the association between snakebite frequency and meteorological parameters. OBJECTIVE: We sought to investigate the seasonality of snakebites and evaluate the association between increasingly common heat waves and other meteorological parameters and snakebite frequency in a semiarid nontropical climate. METHODS: We obtained data for all medical evacuations (2008-2015) because of snakebites in Israel. Climate data included daily 24-hour average temperature (°C) and relative humidity (%). We used a time-stratified case crossover method, in which a conditional logistic regression was applied to estimate the association, and we also stratified our analysis by season and by region. RESULTS: We identified 1234 snakebite cases over 8 years, of which most (74.2%) occurred in hot seasons and between 6 pm and 9 pm. The risk of snakebite was positively associated with temperature >23°C (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.01-1.53) and inversely with humidity >40% (OR 0.74, 95% CI 0.57-0.97). We also found an association with heat waves both in cold (OR 1.62, 95% CI 1.01-2.60) and hot seasons (OR 1.50, 95% CI 1.18-1.92). CONCLUSIONS: In a semiarid nontropical climate, we observed an association between an increase in the number of snakebite cases and higher temperatures and lower humidity. Moreover, heat waves increased the frequency of snakebites in both cold and hot seasons.

Predictive Factors for Death After Snake Envenomation in Myanmar.

INTRODUCTION: Factors predictive for death from snake envenomation vary between studies, possibly due to variation in host genetic factors and venom composition. This study aimed to evaluate predictive factors for death from snake envenomation in Myanmar. METHODS: A prospective study was performed among adult patients with snakebite admitted to tertiary hospitals in Yangon, Myanmar, from May 2015 to August 2016. Data including clinical variables and laboratory parameters, management, and outcomes were evaluated. Multivariate regression analysis was performed to evaluate factors predictive for death at the time of presentation to the hospital. RESULTS: Of the 246 patients with snake envenomation recruited into the study, 225 (92%) survived and 21 (8%) died during hospitalization. The snake species responsible for a bite was identified in 74 (30%) of the patients; the majority of bites were from Russell's vipers (63 patients, 85%). The independent factors predictive for death included 1) duration from bite to arrival at the hospital >1 h (odds ratio [OR]: 9.0, 95% confidence interval [CI]: 1.1-75.2; P=0.04); 2) white blood cell counts >20 ×103 cells·µL-1 (OR: 8.9, 95% CI: 2.3-33.7; P=0.001); and 3) the presence of capillary leakage (OR: 3.7, 95% CI: 1.2-11.2; P=0.02). A delay in antivenom administration >4 h increases risk of death (11/21 deaths). CONCLUSIONS: Patients who present with these independent predictive factors should be recognized and provided with early appropriate intervention to reduce the mortality rate among adults with snake envenomation in Myanmar.

Microangiopathic Hemolytic Anemia Following Three Different Species of Hump-Nosed Pit Viper (Genus: Hypnale) Envenoming in Sri Lanka.

There are 3 species of hump-nosed pit vipers in Sri Lanka: Hypnale hypnale, Hypnale zara, and Hypnale nepa. The latter 2 are endemic to the country. Microangiopathic hemolytic anemia (MAHA) is a known complication of hump-nosed pit viper bites. It was previously documented as a complication of general viper bites and not species specific. We report a series of 3 patients who developed MAHA after being bitten by each species of hump-nosed pit viper. The first patient was bitten by H hypnale and developed a severe form of MAHA associated with acute kidney injury and thrombocytopenia falling into the category of thrombotic microangiopathy. The other 2 developed MAHA that resolved without any complications.

Research Gaps in Wilderness Medicine.

INTRODUCTION: Wilderness medicine involves the treatment of individuals in remote, austere environments. Given the high potential for injuries as well as the unique treatment modalities required in wilderness medicine, evidence-based clinical practice guidelines are necessary to provide optimal care. In this study, we identify evidence gaps from low-quality recommendations in wilderness medicine clinical practice guidelines and identify new/ongoing research addressing them. METHODS: We included relevant clinical practice guidelines from the Wilderness Medical Society and obtained all 1C or 2C level recommendations. Patient/Problem/Population, intervention, comparison, outcome (PICO) questions were created to address each recommendation. Using 24 search strings, we extracted titles, clinical trial registry number, and recruitment status for 8899 articles. We categorized the articles by trial design to infer the effect they may have on future recommendations. RESULTS: Twelve clinical practice guidelines met inclusion criteria. From these we located 275 low-quality recommendations and used them to create 275 PICO questions. Thirty-three articles were relevant to the PICO questions. Heat-related illness had the highest number of relevant articles (n=9), but acute pain and altitude sickness had the most randomized clinical trials (n=6). CONCLUSION: Overall, few studies were being conducted to address research gaps in wilderness medicine. Heat-related illness had the most new or ongoing research, whereas no studies were being conducted to address gaps in eye injuries, basic wound management, or spine immobilization. Animals, cadavers, and mannequin research are useful in cases in which human evidence is difficult to obtain. Establishing research priorities is recommended for addressing research gaps identified by guideline panels.

The Australian Snakebite Project, 2005-2015 (ASP-20).

OBJECTIVE: To describe the epidemiology, treatment and adverse events after snakebite in Australia. DESIGN: Prospective, multicentre study of data on patients with snakebites recruited to the Australian Snakebite Project (2005-2015) and data from the National Coronial Information System. Setting, participants: Patients presenting to Australian hospitals with suspected or confirmed snakebites from July 2005 to June 2015 and consenting to participation. MAIN OUTCOME MEASURES: Demographic data, circumstances of bites, clinical effects of envenoming, results of laboratory investigations and snake venom detection kit (SVDK) testing, antivenom treatment and adverse reactions, time to discharge, deaths. RESULTS: 1548 patients with suspected snakebites were enrolled, including 835 envenomed patients (median, 87 per year), for 718 of which the snake type was definitively established, most frequently brown snakes (41%), tiger snakes (17%) and red-bellied black snakes (16%). Clinical effects included venom-induced consumption coagulopathy (73%), myotoxicity (17%), and acute kidney injury (12%); severe complications included cardiac arrest (25 cases; 2.9%) and major haemorrhage (13 cases; 1.6%). There were 23 deaths (median, two per year), attributed to brown (17), tiger (four) and unknown (two) snakes; ten followed out-of-hospital cardiac arrests and six followed intracranial haemorrhages. Of 597 SVDK test results for envenomed patients with confirmed snake type, 29 (4.9%) were incorrect; 133 of 364 SVDK test results for non-envenomed patients (36%) were false positives. 755 patients received antivenom, including 49 non-envenomed patients; 178 (24%), including ten non-envenomed patients, had systemic hypersensitivity reactions, of which 45 (6%) were severe (hypotension, hypoxaemia). Median total antivenom dose declined from four vials to one, but median time to first antivenom was unchanged (4.3 hours; IQR, 2.7-6.3 hours). CONCLUSIONS: Snake envenoming is uncommon in Australia, but is often severe. SVDKs were unreliable for determining snake type. The median antivenom dose has declined without harming patients. Improved early diagnostic strategies are needed to reduce the frequently long delays before antivenom administration.

Prolonged Coagulopathy, Ecchymoses, and Microangiopathic Hemolytic Anemia Following Hump-Nosed Pit Viper (Hypnale hypnale) Bite in Sri Lanka.

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.