Venom Levels Research Articles

The Effect of a Polyvalent Antivenom on the Serum Venom Antigen Levels of Naja sputatrix (Javan Spitting Cobra) Venom in Experimentally Envenomed Rabbits.

The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab')2 ] at 1hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab')2 and venom antigens, as the terminal half-life and volume of distribution of the F(ab')2 in serum were comparable to that of venom antigens (p>0.05). Infusion of an additional 2ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence.

Detection and neutralization of cobra venom using rabbit antiserum in experimental envenomated mice

A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to detect the venom of Indian cobra (Naja naja naja) in various tissues (brain, heart, lungs, liver, spleen, blood, kidneys, and tissue at the site of injection) of mice after cobra venom injected at different time intervals (0, 2, 4, 6, 8, and 12 h intervals up to 24 h). Whole venom antiserum or individual venom protein antiserum (14, 29, 65, 72, and 99 kDa) could recognize N. n. naja venom by Western blotting and ELISA, and antibody titer was also assayed by ELISA. Antiserum raised against cobra venom in rabbit significantly neutralized the toxicity of venom-injected mice at different time intervals after treatment. The assay could detect N. n. naja venom levels up to 2.5 ng/ml of tissue homogenate, and the venom was detected up to 24 h after venom injection. Venom was detected in brain, heart, lungs, liver, spleen, kidneys, tissue at the bite area, and blood. As observed in mice, tissue at the site of bite area showed the highest concentration of venom and the brain showed the least. Moderate amounts of venoms were found in liver, spleen, kidneys, heart, and lungs. Development of a simple, rapid, and species-specific diagnostic kit based on this ELISA technique useful to clinicians is discussed.

Subacute coagulopathy in a randomized, comparative trial of Fab and F(ab′)2 antivenoms

BackgroundEnvenomation by pit vipers is associated with coagulation disorders including hypofibrinogenemia and thrombocytopenia. These abnormalities correct following antivenom treatment during the acute phase of the disease. Delayed or recurrent coagulation abnormalities have been reported following use of Fab antivenom, resulting in risk of hemorrhage or death. MethodsWe hypothesized that the longer plasma persistence of F(ab′)2 antivenom, relative to Fab, in patients at risk of coagulopathy would result in decreased venonemia and coagulopathy one week after treatment. We conducted a Phase 2, randomized comparative clinical trial of rattlesnake bitten adults presenting for care in Tucson, Arizona, USA. Patients were randomly assigned to receive either Fab or F(ab′)2 antivenom using a predefined treatment schedule. Endpoints included platelet counts, fibrinogen levels, and venom and antivenom ELISAs. Measurements were conducted at baseline and at various times over the following two weeks. ResultsTwelve patients were studied, with 6 randomly assigned to each treatment group. Early response of platelet counts, fibrinogen, and venom levels to acute treatment was similar in the two groups. One week following treatment, platelet counts and fibrinogen levels were lower in the Fab group than in the F(ab′)2 group, following a characteristic pattern that reached its lowest point approximately one week after initial treatment. Venom levels dropped below detection limits in all patients following initial treatment but subsequently rebounded into the measurable range in 4 of 6 Fab cases. F(ab′)2 antivenom levels demonstrated a longer plasma persistence than Fab levels, with a less rapid drop during the two days following treatment. Two patients in the Fab group had significant adverse events involving coagulation abnormalities, for which additional antivenom was administered following the initial treatment period. ConclusionsFollowing the acute phase of presentation and treatment for pit viper envenomation, there appears to be a roughly 2-week subacute phase of the disease during which ongoing presence of venom may result in serious delayed or recurrent coagulation defects. Late hypofibrinogenemia and thrombocytopenia are associated with recurrent venonemia and drop in antivenom levels. This pattern was apparent in patients treated with Fab antivenom but was not seen among F(ab′)2 recipients in this Phase 2 study, consistent with pharmacokinetic differences between the two products. Improved understanding of Fab pharmacokinetics is important for the management of coagulopathy-prone pit viper envenomation. Use of F(ab′)2 antivenom may prevent recurrent venom effects, but larger studies are necessary for statistical confirmation of this observation.

Detection and neutralization of venom of Indian cobra by rabbit antiserum in experimental envenomation using mice

A sandwich enzyme linked immunosorbent assay (ELISA) was developed to detect Indian cobra ( Naja naja naja ) venom in various organs (brain, heart, lungs, liver, spleen, blood, site of injection and kidneys) as well as tissue at the site of injection of mice, at various time intervals (0, 2, 4, 6, 8 and 12 h intervals up to 24 h) after venom injection. Antiserum significantly neutralized venom levels in serum and tissue samples. Whole venom antiserum or individual venom protein anti serum (14 kDa, 29 kDa, 65 kDa, 72 kDa and 99 kDa) of venom could recognize Naja naja venom by Western blotting and ELISA, and Naja naja naja venom presented antibody titer when assayed by ELISA. The assay could detect Naja naja naja venom levels up to 2.5 ng/ml of tissue homogenate and the venom was detected up to 24 h after venom injection. A highly sensitive and species-specifc microtitre ELISA was also developed to detect venoms of four medically important Indian snakes ( Naja naja naja ) in autopsy specimens of mice. Venoms were detected in brain, heart, lungs, liver, spleen, kidneys, tissue at the bite area and blood. As observed in mice, tissue at the site of bite area showed the highest concentration of venom and the brain showed the least. Moderate amounts of venoms were found in liver, spleen, kidneys, heart and lungs. Development of a simple, rapid and species-specifc diagnostic kit based on this ELISA technique useful to clinicians is discussed.

A sensitive enzyme-linked immunosorbent assay for evaluating the concentration of bee venom in rat plasma.

A simple and reproducible enzyme-linked immunosorbent assay (ELISA) was developed to determine the concentration of bee venom in rat plasma. The intra- and inter-assay coefficients of variation for the ELISA were less then 3% between 0.1 and 1,000 ng mL(-1) venom, and the sensitivity of the detection was 0.1 ng mL(-1). Total recovery of the bee venom added to rat plasma was determined. Using this ELISA, serum levels of bee venom were easily determined. The rats were administered a single intravenous injection or oral dose of bee venom (1 mg kg(-1) of body weight). The bioavailability of the bee venom under the two administrations was compared using pharmacokinetic parameters. Results showed that intravenous administration of bee venom produced high plasma concentrations with a short half-life. The area under the curve for oral administration was 10 times lower than for intravenous administration. This loss of bee venom may be due to the degradation that occurs in the enzymatic and acidic environment of the gastrointestinal tract.

Compartment syndrome after Bothrops jararaca snakebite: monitoring, treatment, and outcome

Objective. To report the outcome of a patient who developed compartment syndrome after Bothrops jararaca snakebite. Case report. A 39-year-old male was admitted 5 h after being bitten on the lower right leg. Physical examination revealed tense swelling, ecchymosis, hypoesthesia, and intense local pain that worsened after passive stretching, limited right foot dorsiflexion, and gingival bleeding. The case was classified as moderate/severe and eight vials of bothropic antivenom (AV) were infused 1 h postadmission. The main laboratory findings upon admission were incoagulable blood (incoagulable PT, aPTT, and INR), thrombocytopenia, serum creatine kinase (CK) of 580 U/L (reference value < 170 U/L), and a serum venom level of 33.7 ng/mL (ELISA; cutoff = 2.3 ng/mL). High anterior compartment pressure (60 mmHg) was identified 8 h post bite, with progressively lower pressures after AV administration and limb elevation (36 mmHg; 19 h post bite). However, moderate pain and limited foot dorsiflexion persisted. In addition, there was a progressive increase in serum CK (6,729 U/L; 45 h post bite), as well as marked edema and hemorrhage of the anterior compartment detected by magnetic resonance imaging (MRI) at 48 h post bite. A fasciotomy done after a further increase in intracompartmental pressure (66 mmHg, 57 h post bite) revealed hemorrhage/necrosis of the anterior tibial muscle that subsequently required partial resection. The patient developed a local infection (day 15 post bite) and a permanent fibular palsy. Conclusion. Compartment syndrome is an unusual but severe complication of snakebites. MRI, in conjunction with subfascial pressure measurements, may be useful in the diagnosis of compartment syndrome after snakebites.

Antivenom for Critically Ill Children with Neurotoxicity from Scorpion Stings

Clinically significant scorpion envenomation by Centruroides sculpturatus produces a dramatic neuromotor syndrome and respiratory insufficiency that often necessitate intensive supportive care. We hypothesized that a scorpion-specific F(ab')(2) antivenom would promptly resolve clinical symptoms in children with this syndrome. In a randomized, double-blind study, the efficacy of scorpion-specific F(ab')(2) antivenom, as compared with placebo, was assessed in 15 children 6 months to 18 years of age who were admitted to a pediatric intensive care unit with clinically significant signs of scorpion envenomation. The primary end point was the resolution of the clinical syndrome within 4 hours after administration of the study drug. Secondary end points included the total dose of concomitant midazolam for sedation and quantitative plasma venom levels, before and after treatment. The clinical syndrome resolved more rapidly among recipients of the antivenom than among recipients of placebo, with a resolution of symptoms in all eight antivenom recipients versus one of seven placebo recipients within 4 hours after treatment (P=0.001). More midazolam was administered in the placebo recipients than in the antivenom recipients (mean cumulative dose, 4.61 vs. 0.07 mg per kilogram of body weight; P=0.01). Plasma venom concentrations were undetectable in all eight antivenom recipients but in only one placebo recipient 1 hour after treatment (P=0.001). Among critically ill children with neurotoxic effects of scorpion envenomation, intravenous administration of scorpion-specific F(ab')(2) antivenom resolved the clinical syndrome within 4 hours, reduced the need for concomitant sedation with midazolam, and reduced the levels of circulating unbound venom. (ClinicalTrials.gov number, NCT00685230.)

Serum levels and urine detection of Centruroides sculpturatus venom in significantly envenomated patients

Introduction. Envenomation by Centruroides sculpturatus can cause systemic signs and symptoms requiring treatment. The toxicokinetics of C. sculpturatus venom has not been described. Methods. Venom components were separated for cross-reactivity testing. Serum and urine collected from three patients envenomated by C. sculpturatus had venom levels determined by sandwich enzyme-linked immunosorbent assay (ELISA). Results. Western blot analysis indicated recognition of C. sculpturatus venom by Alacramyn®, an equine F(ab′)2 antivenom developed against Centruroides scorpion venoms, including C. sculpturatus. Serum venom levels in ng/mL with post-envenomation times in minutes (min) were as follows: 85-year-old woman = 8.2 (∼150), 2.8 (515), 1.6 (1,200); 14-month-old girl = 29.7 (∼50), 5.0 (729); 3-year-old girl = 11.1 (∼313), urine venom level of 9.0 (∼490). Conclusion. There is sufficient venom cross-antigenicity among different Centruroides species to allow this ELISA technique with Alacramyn® to determine serum and urine C. sculpturatus venom concentrations in envenomated patients.

Serum kinetics of Calloselasma rhodostoma (Malayan pit viper) venom components in a rabbit

The serum kinetics of Calloselasma rhodostoma (Malayan pit viper) venom - specifically two of its components, the major hemorrhagin (rhodostoxin) and a thrombin-like enzyme - was examined in a rabbit by double-sandwich enzyme-linked immunosorbent assay (ELISA). The animal received intramuscularly a 1.0-mg/kg dose of C. rhodostoma venom. The venom level in serum peaked 12 hours after the injection, followed by a gradual decline and finally reached low rates 72 hours after administration. The serum kinetic profile of venom components, however, did not correspond to the profile of the whole C. rhodostoma venom. The serum levels of the C. rhodostoma thrombin-like enzyme increased slowly and peaked only 48 hours post-injection. Then both thrombin-like enzyme and rhodostoxin remained at relatively high levels 72 hours after administration. Data suggest that various venom components bind to tissue at the injection site with different affinities and that conjugated venom components were continuously released into circulation at different rates. The prolonged high serum levels of both thrombin-like enzyme and hemorrhagin are consistent with the clinical picture of prolonged clotting deficiency in severe cases of C. rhodostoma envenomation. Our results also suggest that since venom components are being released into and eliminated from the circulation at different rates, the "average composition" of the venom antigen in the circulation changes over time. This implies that data from ELISA quantification of antigen levels from serum venom employing "whole venom" as reagent must be interpreted with care.

Kinetics of venom and antivenom serum levels, clinical evaluation and therapeutic effectiveness in dogs inoculated with Crotalus durissus terrificus venom

This work evaluated the clinical and therapeutic aspects as well as serum levels of venom and antivenom IgG by enzyme-linked immunosorbent assay (ELISA) in experimental envenomation of dogs with Crotalus durissus terrificus venom. Twenty-eight mixed breed adult dogs were divided into four groups of seven animals each, Group I: only venom; Group II, venom + 50 ml of anti-bothropic-crotalic serum (50mg) + fluid therapy; Group III, venom + 50 ml of anti-bothropic-crotalic serum + fluid therapy + urine alkalination; Group IV, 50 ml of anti-bothropic-crotalic serum. The lyophilized venom of Crotalus durissus terrificus was reconstituted in saline solution and subcutaneously inoculated at the dose of 1mg/kg body weight. The dogs presented clinical signs of local pain, weakness, mandibular ptosis, mydriasis, emesis and salivation. The venom levels detected by ELISA ranged from 0 to 90ng/ml, according to the severity of the clinical signs. Serum antivenom ranged from 0 to 3ug/ml and was detected for up to 138h after treatment. ELISA results showed the effectiveness of the serum therapy for the venom neutralization.

Role of IgG(T) and IgGa isotypes obtained from arachnidic antivenom to neutralize toxic activities of Loxosceles gaucho, Phoneutria nigriventer and Tityus serrulatus venoms

The ability of IgG(T) and IgGa subclasses—isolated by liquid chromatography from equine arachnidic antivenom (AAV)—to neutralize toxic activities of Loxosceles gaucho, Phoneutria nigriventer and Tityus serrulatus venoms as well as to remove venom toxins from circulation was investigated. These subclasses showed similar antibody titers against L. gaucho, P. nigriventer and T. serrulatus venoms, and by immunoblotting few differences were observed in the recognition pattern of venom antigens. IgG(T) and IgGa neutralized 100% lethality induced by L. gaucho and 50% of P. nigriventer venom, but IgGa failed to neutralize T. serrulatus venom, in contrast to IgG(T). Both subclasses neutralized local reactions and dermonecrosis induced by L. gaucho venom in rabbits. In mice, IgG(T) and IgGa partially neutralized the edematogenic activity induced by P. nigriventer and T. serrulatus venoms, but only IgG(T) neutralized (ca. 81%) the nociceptive activity induced by T. serrulatus venom. Both subclasses failed to neutralize nociceptive activity induced by P. nigriventer venom. IgG(T) reduced the serum venom levels of animals injected with L. gaucho, P. nigriventer or T. serrulatus venoms, while IgGa solely reduced L. gaucho and P. nigriventer venoms levels. Our results demostrate that IgG(T) and IgGa subclasses neutralize toxic activities induced by P. nigriventer, T. serrulatus and L. gaucho venoms with different efficacies, as well as depurate these venoms from circulation.

Treatment of snakebite in Australia: The current evidence base and questions requiring collaborative multicentre prospective studies

Despite the wealth of anecdotes and case reports there are fundamental questions of management of snakebite in Australia that remain unresolved or for which the current evidence is limited. The efficacy in the field, potential limitations and possibility of improvements in pressure immobilisation first aid need objective studies in humans. Optimal bandage sizes, stretch and pressure for different sized limbs need further evaluation, as does the use of pressure pads. Better definitions of specific clinical envenoming syndromes attributable to individual snake species are required, including elucidation of within-genus variations, similarities and differences. Venom studies suggest this is especially important for species within the brown snake ( Pseudonaja) and death adder ( Acanthophis) genera. Appropriate antivenom types, doses and dosing intervals for individual snake species should be more formally studied in patients. Especially important are confirmation of the need for higher doses of brown snake antivenom, while possibly limiting unnecessarily high doses, confirmation of the critical importance of early antivenom use to prevent pre-synaptic neurotoxicity in Taipan and tiger snake bites and ascertainment of whether larger doses of antivenom are unhelpful in Taipan bites after specified time delays. Confirmation of clinical efficacy and dosing recommendations for use of tiger snake ( Notechis) antivenom in envenoming from Australian copperhead ( Austrelaps spp.), broad headed ( Hoplocephalus spp.) and rough-scaled snakes ( Tropidechis carinatus) also require formal study in patients. Other examples of clinical relevance of cross-specificity of current and future monospecific antivenoms and whether there are geographical variations in antivenom responses within species will require elucidation. Prospective multicentre collaborative studies with predefined data collection and serial venom level assays are proposed as the way forward in Australia to help resolve therapeutic uncertainties and to establish a firmer evidence base for best-practice treatment guidelines for Australasian elapid snakebite.

A randomized, double-blind, placebo-controlled trial of antivenom for local effects of green pit viper bites

Although systemic administration of antivenom can promptly reverse coagulopathy, efficacy on local effects of viper venom remains to be determined. Currently, there has been no proven specific treatment for snakebite patients with severe local effects. This study is a randomized, double-blind, placebo-controlled trial. Patients bitten by green pit vipers (Trimeresurus albolabris or T. macrops) with marked limb swelling, but no severe coagulopathy requiring antivenom, were randomized to receive either equine F(ab')2 antivenom, or placebo. Twenty-eight cases were included, 14 in each group, and they had their limb circumferences measured on days 1, 2, 4 and 6 after interventions. The percentage reduction in limb circumference was significantly better in the antivenom group compared with the placebo group (ANOVA, P = 0.03), especially in the first 24 h (1.14 vs. 3.62%, in placebo and antivenom group, respectively, P = 0.014). The reduction in pain score was similar. The plasma venom levels were not different at presentation but lower in the antivenom group 24h after intervention (P = 0.033). These data suggest that intravenous antivenom could accelerate local oedema resolution in humans. However, the degree is not clinically significant, and, therefore, general use is not recommended.

Detection and neutralization of venom by ovine antiserum in experimental envenoming by Bothrops jararaca

In this study we optimized an enzyme-linked immunosorbent assay (ELISA) to evaluate bothropic venom levels in biological samples. These samples were obtained by two distinct protocols. In the first one, Swiss mice were injected with 1 LD50 of Bothrops jararaca (B. jararaca) venom and 15 minutes later, animals were treated with ovine antibothropic serum. Blood and spleen homogenate samples were obtained 6 hours after antiserum therapy. Ovine antibothropic serum significantly neutralized venom levels in serum and spleen. In the second protocol, BALB/c mice were injected with 1 LD50 of bothropic venom by either intraperitoneal (IP) or intradermal (ID) route and venom levels were evaluated 1, 3 and 6 hours after, in blood, spleen homogenates and urine. Serum and splenic venom levels were significantly higher in animals envenomed by IP route comparing with animals envenomed by ID route. Higher venom levels were also detected in urine samples from animals envenomed by IP route. However, these differences were not statistically significant. These results demonstrated that the optimized ELISA was adequate to quantify venom levels in different biological samples. This assay could, therefore, substitute the in vivo neutralizing assay and also be useful to evaluate the severity of human and experimental envenomations.

Antivenom treatment and renal dysfunction in Russell's viper snakebite in Taiwan: a case series

Formosan Russell's viper (Daboia russelli siamensis) is the sixth most frequent cause of snakebites in Taiwan. Its bite induces greater kidney injury than other Russell's vipers in Southeast Asia. Poor availability of antivenom might be the major reason. To enhance treatment, we supplied the antivenom to the teaching hospitals that are near the areas where D. r. siamensis is found. We also used an ELISA in diagnosis. From June 1999 to December 2001, a total of 13 cases of D. r. siamensis snakebite were diagnosed with serum venom level of 10-98 ng/ml, 1-6 hours after being envenomed. Abnormal coagulation function and acute renal failure occurred early and were the two most important clinical features. Early specific antivenom treatment, 3-6 hours after systemic envenoming, restored the coagulation function in 1-2 days and seemed to be statistically effective in reducing the severity of renal damage compared with the historical and delayed group by the Wilcoxon rank-sum test. Two to four vials of antivenom were needed to block the systemic toxicity and produced few side effects. The antivenom should be administered as early as possible to prevent systemic dysfunction.

Assessment of the neutralizing potency of ovine antivenom in a swiss mice model of Bothrops jararaca envenoming

Alternative sources of anti-ophidic serum are being investigated due to the secondary effects associated with types I and II hypersensitivity reactions. In the present study we raised and evaluated the protective effect of an ovine antibothropic serum in a Swiss mice envenoming model. Ovine antiserum was obtained by immunization with seven increasing doses of bothropic venom associated with adjuvants. The neutralizing ability was tested by the lethal activity (2 LD50) neutralization and serum and splenic venom levels after antivenom administration to experimentally envenomed mice. The antiserum effect on local edema was also tested by injection of venom/antivenom mixtures into the mice footpads. Ovine antiserum neutralized lethal activity and also significantly decreased serum and splenic venom levels. However, this antiserum was not able to mediate any protective effect on edema triggered by bothropic venom.

The kinin system in the envenomation caused by the Tityus serrulatus scorpion sting

Several lines of evidence in experimental animals indicate that the kinin system may participate in the pathogenesis of envenomation by the Tityus serrulatus (Ts) scorpion sting, but there are no studies in humans with regard to this system. In this study, we evaluated the plasma levels of high-molecular (HKg) and low-molecular (LKg) weight kininogens (detected by ELISA), the activities of plasma or tissue kallikreins and kininase II (enzymatic action upon selective substrates), and the Ts plasma venom levels (ELISA). A total of 27 patients (12 males) aged 12–72 were evaluated immediately at hospital admittance. According to the severity of envenomation, patients were classified as mild ( n = 15), moderate ( n = 8), and severe cases ( n = 4). Controls were paired for age and sex. Plasma venom levels were associated with the severity of envenomation. Severe cases presented lower levels of LKg in relation to mild and controls. Inverse correlations were seen between LKg levels and the venom concentration. The results of this study suggested that the kinin system may participate in the pathogenesis of human Ts envenomation and knowledge about this system may be useful to develop new strategies to reduce the damage caused by scorpion envenomation.

The clinical significance of venom detection in patients of cobra snakebite

Cobra snakebites are one of the most frequent occurrences among the poisonous snakebites. The correlation between the serum concentrations of cobra venom in the victims with the severity of systemic and local symptoms after envenoming is still awaited for investigation. In this paper, we have developed an enzyme-linked immunosorbent assay (ELISA) to detect Taiwan cobra venom existed in the serum of the cobra snakebite victims. This established technique allowed us to detect as low as 1 ng/ml. Totally, 31 serum samples of 27 recognized and suspected cobra snakebite patients were analyzed by the developed ELISA technique. The highest venom level detected was 1270 ng/ml in a case 2 h after being envenomed. We found that the serum concentrations of the venom in the bitten patients were well correlated with the severity of local tissue destruction. Venom levels might remain high 48 h after snakebite. Two or more vials of specific antivenom administered soon after snakebite were effective in neutralizing the circulating venom as revealed by ELISA. Higher doses of antivenom may be indicated in cases of cobra venom-induced local tissue destruction. In conclusion, these results indicate that venom detection in snakebite victims is valuable in diagnosis and severity assessment of Taiwan cobra snakebite.

Antivenom treatment in arachnidism.

Envenomation by arachnids causes significant medical illness worldwide. Scorpion sting is the most important arachnid envenomation causing adult morbidity and pediatric mortality. Important groups of spiders include the widow spiders (Latrodectus spp.), the recluse spiders (Loxosceles spp.), and two spiders confined to single countries: the Australian funnel web spider (Atrax and Hadronyche spp.) and the armed spider (Phoneutria spp.) from Brazil. There are four widow spider antivenoms available, including the Australian redback spider antivenom and the American black widow antivenom. Despite good in vitro animal work demonstrating effective neutralization with these antivenoms, and cross-reactivity between many species, there continues to be a reluctance to use them in some countries. They are both associated with a relatively low rate of allergic reactions. Redback antivenom is routinely used by the intramuscular route, which may not be as effective as intravenous use based on clinical experience and animal studies. Antivenoms are available for Loxosceles spp., but there is little evidence to support their effectiveness, particularly against local effects. The Australian funnel web spider causes severe neurotoxic envenomation, and antivenom appears to be effective in reported cases. An antivenom exists for the Brazilian armed spider, but is used in only a minority of cases. Many scorpion antivenoms exist worldwide, but there remains significant controversy regarding their efficacy. Animal and human venom level studies demonstrate neutralization of circulating venom in systemic envenomation. Clinical experience in countries where antivenom has been introduced suggests it has reduced pediatric mortality. However, three controlled trials demonstrated that antivenom was not effective, but these included few severe cases. Until controlled trials of antivenom in systemically envenomated patients are undertaken, antivenom use appears justified in severe envenomation. Although envenomation from arthropods is common, no antivenoms exist for these, excepting Lonomia caterpillars in South America, and Ixodes paralysis ticks in Australia.

Relationship between plasmatic levels of various cytokines, tumour necrosis factor, enzymes, glucose and venom concentration following Tityus scorpion sting

A sandwich enzyme-linked immunosorbent assay was developed for measuring Tityus venom levels in plasma. The method proved capable of distinguishing patients with only local symptoms from controls, and was used to quantify venom in 205 accidental human envenomations. Our results show that the severity of envenoming is related to the patient plasma venom concentration. This depends on time elapsed between the sting and when the plasma was drawn. We observed that 46 and 49% of patients with moderate to severe symptoms (MS, n=41) showed hyperamylasemia and hyperglycemia, respectively. In addition, 39% of cases with MS symptoms had partial thromboplastin time values prolonged or shorted and 6.5% of patients with local symptoms (LS, n=164) had only prolonged prothrombin time values. Interleukin6 (IL6) increased significantly in patients with MS symptoms. IL6 values increased with hyperamylasemia, envenoming severity and time hyperamylasemia.