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BACKGROUND/OBJECTIVE: Although evidence of scorpion antivenin effectiveness in the clinical setting is lacking, scorpion antivenin is generally considered the only specific treatment for scorpion sting irrespective of its clinical severity. We conducted a matched-pair study to assess the efficacy of systematic administration of scorpion antivenin. METHODS: Among 600 stung patients who participated in a study on the efficacy of high-dose hydrocortisone after scorpion sting, 135 (cases) had been treated with 10 to 20 mL intravenous scorpion antivenin (neutralizing 10 LD50 venom/mL). Controls were matched on disease severity on arrival to the emergency department. The severity of envenomation was graded I or II according to the absence (grade I) or the presence (grade II) of systemic manifestations of scorpion envenomation. Assessment of scorpion antivenin efficacy was based on the rate of changing severity grade in both groups (clinical improvement or worsening during an observation period of at least 4 hours). RESULTS: Both groups were similar with respect to clinical severity (36 patients were graded II in each group), age, sex, time-lapse between scorpion sting and ED arrival, and the administration of adjunctive therapy such as hydrocortisone. By the 4-hour evaluation, 50% and 64% of patients initially graded II exhibited a substantial clinical improvement in cases and controls, respectively, suggesting similar effects in cases and controls. There was no difference in preventive effects: 13% and 10% of cases and controls developed systemic manifestations of scorpion envenomation during the 4-hour observation period; 23% of cases and 17% controls were hospitalized by this time. There was no difference in the duration of hospitalization. Three cases developed anaphylactic shock as a consequence of scorpion antivenin administration, while 1 scorpion antivenin-untreated patient died from refractory shock. CONCLUSION: Systematic administration of scorpion antivenin irrespective of clinical severity did not alter the clinical course of scorpion sting. A prospective study is needed concerning the response of the more severe scorpion envenomations.
BACKGROUND: The common striped scorpion, Centruroides vittatus, and the imported fire ant (IFA) are endemic to the south-central United States. There is evidence of venom-specific IgE in patients experiencing hypersensitivity reactions to scorpion stings. The infrequency of repeated scorpion stings and the presence of immediate reactions to an initial sting suggest prior sensitization. OBJECTIVE: In the present study we evaluated the cross-reactivity of C vittatus venom with IFA whole-body extract (WBE). METHODS: Sera were obtained from patients with symptoms of immediate hypersensitivity to C vittatus stings and from scorpion sting-naive patients allergic to IFA venom. Inhibition IgE immunoblots were performed by using scorpion venom and IFA WBE. Skin testing with scorpion venom was performed on scorpion sting-naive patients allergic to IFA venom. RESULTS: Sera from patients with scorpion venom allergy demonstrated IgE binding to multiple allergens of similar sizes against both scorpion venom and IFA WBE. This binding was completely inhibited by preincubation of the sera with scorpion venom and IFA WBE. Pooled sera from patients with IFA venom allergy demonstrated similar bands on IgE immunoblotting against both IFA WBE and scorpion venom, with the latter being completely inhibited by preincubation of the sera with IFA WBE. Skin testing with scorpion venom was positive in 6 of 9 patients with IFA venom allergy. CONCLUSION: Significant cross-reactivity exists between the venom of C vittatus and IFA WBE. The high sensitization rate to IFA venom in endemic areas may therefore be a risk factor for subsequent immediate reactions to an initial scorpion sting. Patients with immediate hypersensitivity reactions to scorpion stings may potentially benefit from immunotherapy with IFA WBE.
BACKGROUND: Evidence for the benefit of scorpion antivenom, the only specific treatment for scorpion envenomation, is scarce, despite its common use. We did a prospective, randomised, controlled trial to assess the efficacy of routine administration of scorpion antivenom to scorpion-stung patients, irrespective of clinical severity. METHODS: We included 825 consecutive patients older than 10 years, who presented to the accident and emergency department of the hospital in Tozeur, Tunisia. We graded severity by absence (grade I) or presence (grade II) of systemic manifestations of scorpion envenomation. Patients were randomly assigned placebo (n=413) or 20 mL bivalent intraveneous scorpion antivenom (n=412). All patients were observed for 4 h. Patients who developed life-threatening symptoms were admitted to the intensive-care unit. At the end of 4 h observation we reassessed grade and discharged grade II patients and admitted grade II patients. We assessed the preventive and curative effects of scorpion antivenom by prevention of worsening grade or by improvement from grade II to grade I. FINDINGS: Distribution of severity grades was similar in the two groups at baseline, as were the cure rates (55% scorpion antivenom, 66% placebo, absolute difference, 11% [95% CI -4.8 to 26.8]; p=0.234). Preventive effects were seen in 94% and 96% of patients in the scorpion antivenom and placebo groups, respectively, who were initially grade I and who remained symptom-free (absolute difference, 2% [-1.27 to 5.27]; p=0.377). Time from scorpion sting to administration of scorpion antivenom did not affect curative and preventive effects. INTERPRETATION: We found no benefit in routine administration of scorpion antivenom after scorpion sting, irrespective of clinical severity. Future studies should focus on patients with the most severe symptoms and signs.
Scorpion stings cause more morbidity in Mexico than any other country, leading to about 100 deaths annually. In 1999, the State of Morelos reported nine deaths among 30663 cases of scorpion sting. To replace lindane used for scorpion control, field trials of pyrethroid pesticides were undertaken in Morelos during 1998-2000 at the village of Chalcatzingo (population initially with 2760 inhabitants and 530 houses). Pre-intervention surveys detected scorpions (Scorpiones: Buthidae) of two species in the majority of houses: Centruroides limpidus limpidus Karsch outnumbering Vaejovis mexicanus smithi Koch. Scorpion prevalence was assessed, pre- and post-spray, directly by searching (40 min/house) and by householder reports of sightings inside houses. Pre-intervention perceptions of scorpion abundance were similar for all areas, with sightings in 12-18% of houses, whereas daytime searches detected more infestations in eastern parts of the village (prevalence 17% indoors, 22% outdoors) than in other sectors (9% indoors, 14% outdoors). Pyrethroids were evaluated as residual treatments in separate sectors of Chalcatzingo, with almost complete coverage indoors and peridomestically, using the following four formulations: bifenthrin 10% wettable powder (WP) applied at 50mg a.i./m2, cyfluthrin 10% WP (Solfac 10 WP) at 44-55 mg a.i./m2, deltamethrin 2.5% suspension concentrate (Biothrin 25 SC) at 11 mg a.i./m2 and 5% WP (K-Othrine 50 WP) at 35 mg a.i./m2. Phase 1 compared bifenthrin 10 WP, Solfac 10 WP and Biothrin 25 SC sprayed in December 1998; phase 2 compared Solfac 10 WP and K-Othrine 50 WP sprayed in June and again in December 2000, with follow-up surveys of scorpions one month post-spray and subsequently. Scorpion prevalence was reduced by 64-77% peridomestically one month post-spray and by 83, 46 and 15% in houses sprayed with cyfluthrin WP, bifenthrin WP or deltamethrin SC, respectively. Householder reports of sighting scorpions indoors were 33-85% below pre-intervention levels. Cumulative effects of the three spray-rounds over 3 years reduced scorpion prevalence by approximately 60% in the deltamethrin WP re-sprayed area and by approximately 90% in the cyfluthrin WP re-sprayed area. Householder sightings also fell by 67 and 28% in the cyfluthrin and delta-methrin re-sprayed areas, respectively. Operational efficacy of these products against scorpions at the dosages applied was ranked as cyfluthrin WP > bifenthrin WP > deltamethrin SC > WP. Reported cases of scorpion sting intoxication fell by 17% during this study after having risen by approximately 40% over four previous years.
All scorpion toxins from different 30 species are simply reviewed. A new classification system of scorpion toxins is first proposed: scorpion toxins are classified into three families (long-chain scorpion toxins with 4 disulfide bridges, short-chain scorpion toxins with 3 disulfide bridges, and intermediate-type scorpion toxins with 3 or 4 disulfide bridges). Intermediate-type scorpion toxins provide a strong proof for the conclusion that channel toxins from scorpion venoms evolve from a common ancestor. Common organization of precursor nucleotides and genomic sequence, similar 3-dimensional structure, and the existence of intermediate type scorpion toxins and functionally intercrossing scorpion toxins show that all scorpion toxins affecting ion channels evolve from the common ancestor, which produce millions of scorpion toxins with function-diversity.
OBJECTIVE: To describe the epidemiological and clinical features of scorpion stings in a district with potentially lethal scorpions. DESIGN: Case series of consecutive scorpion sting victims. SETTING: Manama Hospital and all seven rural health centres in Gwanda South District, Zimbabwe (population 62500). PARTICIPANTS: All known cases of scorpion sting reporting to health centres in the district; all severe cases in which the scorpions had been identified, and who were admitted and examined by the author between September 1991 and September 1993. MAIN OUTCOME MEASURES: Description of clinical features of severe Parabathus transvaalicus scorpionism. RESULTS: Two hundred and forty-four cases, of which 184 were P. transvaalicus Purcell, 1899. Seventeen patients with severe P. transvaalicus scorpionism showed sensory and motor nerve stimulation, with generalised hyperaesthesia, weakness, ptosis, dysphagia, muscle tremors and abnormal reflexes. There was cardiac involvement, and respiration was compromised secondary to muscular weakness. Parasympathetic nervous system stimulation was seen in the absence of sympathetic stimulation, with profuse sialorrhoea, sweating and urinary retention. CONCLUSIONS: The clinical features of P. transvaalicus scorpionism are described for the first time. These resemble those of P. granulatus scorpionism which, however, has significant sympathetic nervous system stimulation, the distinguishing features being visual disturbances, anxiety, restlessness and raised blood pressure. Scorpion antivenom should be given for both. General recommendations on management of scorpion stings are given.
Sodium channels posses receptor sites for many neurotoxins, of which several groups were shown to inhibit sodium current inactivation. Receptor sites that bind alpha- and alpha-like scorpion toxins are of particular interest since neurotoxin binding at these extracellular regions can affect the inactivation process at intramembranal segments of the channel. We examined, for the first time, the interaction of different scorpion neurotoxins, all affecting sodium current inactivation and toxic to mammals, with alpha-scorpion toxin receptor sites on both mammalian and insect sodium channels. As specific probes for rat and insect sodium channels, we used the radiolabeled alpha-scorpion toxins AaH II and LqhalphaIT, the most active alpha-toxins on mammals and insect, respectively. We demonstrate that the different scorpion toxins may be classified to several groups, according to their in vivo and in vitro activity on mammalian and insect sodium channels. Analysis of competitive binding interaction reveal that each group may occupy a distinct receptor site on sodium channels. The alpha-mammal scorpion toxins and the anti-insect Lqh alphaIT bind to homologous but not identical receptor sites on both rat brain and insect sodium channels. Sea anemone toxin ATX II, previously considered to share receptor site 3 with alpha-scorpion toxins, is suggested to bind to a partially overlapping receptor site with both AaH II and Lqh alphaIT. Competitive binding interactions with other scorpion toxins suggest the presence of a putative additional receptor site on sodium channels, which may bind a unique group of these scorpion toxins (Bom III and IV), active on both mammals and insects. We suggest the presence of a cluster of receptor sites for scorpion toxins that inhibit sodium current inactivation, which is very similar on insect and rat brain sodium channels, in spite of the structural and pharmacological differences between them. The sea anemone toxin ATX II is also suggested to bind within this cluster.
alpha-Scorpion toxins and sea anemone toxins bind to a common extracellular site on the Na+ channel and inhibit fast inactivation. Basic amino acids of the toxins and domains I and IV of the Na+ channel alpha subunit have been previously implicated in toxin binding. To identify acidic residues required for toxin binding, extracellular acidic amino acids in domains I and IV of the type IIa Na+ channel alpha subunit were converted to neutral or basic amino acids using site-directed mutagenesis, and altered channels were transiently expressed in tsA-201 cells and tested for 125I-alpha-scorpion toxin binding. Conversion of Glu1613 at the extracellular end of transmembrane segment IVS3 to Arg or His blocked measurable alpha-scorpion toxin binding, but did not affect the level of expression or saxitoxin binding affinity. Conversion of individual residues in the IVS3-S4 extracellular loop to differently charged residues or to Ala identified seven additional residues whose mutation caused significant effects on binding of alpha-scorpion toxin or sea anemone toxin. Moreover, chimeric Na+ channels in which amino acid residues at the extracellular end of segment IVS3 of the alpha subunit of cardiac Na+ channels were substituted into the type IIa channel sequence had reduced affinity for alpha-scorpion toxin characteristic of cardiac Na+ channels. Electrophysiological analysis showed that E1613R has 62- and 82-fold lower affinities for alpha-scorpion and sea anemone toxins, respectively. Dissociation of alpha-scorpion toxin is substantially accelerated at all potentials compared to wild-type channels. alpha-Scorpion toxin binding to wild type and E1613R had similar voltage dependence, which was slightly more positive and steeper than the voltage dependence of steady-state inactivation. These results indicate that nonidentical amino acids of the IVS3-S4 loop participate in alpha-scorpion toxin and sea anemone toxin binding to overlapping sites and that neighboring amino acid residues in the IVS3 segment contribute to the difference in alpha-scorpion toxin binding affinity between cardiac and neuronal Na+ channels. The results also support the hypothesis that this region of the Na+ channel is important for coupling channel activation to fast inactivation.
Photoreactive derivatives of alpha- and beta-scorpion toxins have been used to analyze the subunit composition of Na+ channels in rat brain. In synaptosomes, both types of toxins preferentially labeled (greater than 85%) a component of 34,000 Da and, at a lower level, another component of 300,000 Da. Reduction of disulfide bridges shifted this latter band from 300,000 Da to 272,000 Da but did not modify the migration of the 34,000-Da component. Similarly, two bands were labeled in cultured brain neurons, one at 259,000 Da by alpha-scorpion toxins and the other at 34,000 Da by both alpha- and beta-scorpion toxins. Contrary to what was observed in synaptosomes, in cultured brain neurons reduction of disulfide bridges had no effect on the migration of the labeled high molecular weight component. Labeling of the smaller polypeptide was obtained even when cells were solubilized with sodium dodecyl sulfate immediately after cross-linking which proves that the 34,000-Da component is not a product of proteolysis. Binding sites for alpha- and beta-scorpion toxins, respectively, did not develop in parallel during neuronal maturation in culture: the increase in beta-scorpion toxin-binding site density was lower and later than that for alpha-scorpion toxin. When related to morphological development, the increase in alpha-scorpion toxin-binding sites was correlated to neurite growth, whereas the increase in beta-scorpion toxin-binding sites was associated with the development of chemical synapses. Finally, in cultured neurons, but not in synaptosomes, both the binding of beta-scorpion toxin and the labeling of the 34,000-Da component by beta-scorpion toxin were enhanced by depolarization of the cell membrane.
1. The autonomic effects of venoms and toxins from several species of scorpions, including the Indian red scorpion Mesobuthus tamulus, the Chinese scorpion Buthus martensi Karsch and the Israeli scorpion Leiurus quinquestriatus quinquestriatus, all belonging to Buthidae, and the Asian black scorpions Heterometrus longimanus and Heterometrus spinifer, belonging to Scorpionidae, are reviewed. 2. The effects of the venoms of M. tamulus and L. q. quinquestriatus on noradrenergic and nitrergic transmission in the rat isolated anococcygeus muscle revealed that both venoms mediated their pharmacological effects via a prejunctional mechanism involving the activation of voltage-sensitive sodium channels with consequent release of neurotransmitters that mediate target organ responses, similar to the effects mediated by other alpha-scorpion toxins. 3. Two new toxins, Makatoxin I and Bukatoxin, were purified to homogeneity from the venom of B. martensi Karsch. Determination of their complete amino acid sequences confirmed that both toxins belonged to the class of alpha-scorpion toxins. The effects of both toxins on noradrenergic and nitrergic transmission in the rat anococcygeus muscle provided firm evidence that their pharmacological actions also closely resembled those mediated by other alpha-scorpion toxins on neuronal voltage-sensitive sodium channels. 4. The venoms of H. longimanus and H. spinifer were found to have high concentrations of noradrenaline (1.8 +/- 0.3 mmol/L) and relatively high concentrations of acetylcholine (79.8 +/- 1.7 micromol/L) together with noradrenaline (146.7 +/- 19.8 micromol/L), respectively, which can account for their potent direct cholinergic and noradrenergic agonist actions in the rat anococcygeus muscle. 5. Our studies confirmed that the rat anococcygeus muscle is an excellent nerve-smooth muscle preparation for investigating the effects of bioactive agents on noradrenergic and nitrergic transmission, as well as the direct agonist actions of these agents on post-synaptic alpha-adrenoceptors and M3 muscarinic cholinoceptors. Although many studies, including our own, have documented that scorpion venoms and toxins mediate their primary effects via a prejunctional mechanism that leads to the marked release of various autonomic neurotransmitters, our studies have shown that there are exceptions to this generally accepted phenomenon. In particular, we have provided firm evidence to show that the venoms from H. longimanus and H. spinifer do not have such a prejunctional site of action but, instead, the venoms mediate their autonomic effects through direct agonist actions on post-junctional muscarinic M3 cholinoceptors and alpha-adrenoceptors.
Despite scorpions being locally abundant in many parts of Australia, scorpion sting is a poorly defined clinical condition in Australia. Many health-care workers are unaware of the effects of their stings and scorpions are often feared based on their international reputation. Five scorpion stings that occurred in different parts of Australia where the scorpion was caught at the time of the sting and identified by a professional arachnologist are reported in the present paper. The spectrum of clinical effects of scorpion stings in Australia and the potential for significant effects are discussed. These cases and recent prospective case series demonstrate that in Australia scorpion stings cause only minor effects. The main effect is localized pain lasting for several hours, associated less commonly with systemic effects, local numbness and paraesthesia. Most stings are from smaller scorpions from the family Buthidae and often occur indoors at night. The stings from Australian buthid scorpions cause more severe effects than from the larger species in the families Urodacidae (genus Urodacus) and Liochelidae (genus Liocheles).
There is little information on scorpion stings in Australia. The aim of this study is to describe the circumstances and clinical effects of stings by Australian scorpions. Cases of scorpion stings were collected prospectively from calls and presentations to Australian poison information centres and emergency departments from February 2000 to April 2002. Only definite scorpion stings where the scorpion was immediately collected and expertly identified were included. There were 95 patients, 33 males and 62 females, with a mean age of 32 (SD 19.5; range 1-71) and 23 children (age<15 years). Three families of scorpions caused all stings: Buthidae (79), Bothruiridae (11, all Cercophonius spp.) and Urodacidae (five, all Urodacus spp.). The majority of stings (76%) were by one genus of scorpion Lychas spp. Seventy one percent of stings occurred between 6pm and 8am and 82 (86%) occurred indoors. Sixty percent of stings occurred on distal limbs. The median duration of effects was 6 h (interquartile range (IQR): 1-24 h). Immediate localised pain occurred in all cases and was severe in 76 cases (80%). Other local effects included red mark/redness (66%), tenderness (35%), numbness (12%) and paraesthesia (11%). Minor systemic effects (nausea, headache and malaise) occurred in 11% of cases. There were no deaths or major systemic envenoming. Less severe effects were observed for the larger Urodacus species, compared to Lychas spp. Scorpion stings in Australia do not appear to cause severe or life-threatening effects, even in children. This differs from other parts of the world, where severe envenoming is reported. The major clinical effect is severe pain, consistent with other scorpion stings. Most stings occurred indoors and at night.
Electrophysiological analysis of the effects of scorpion toxin I, one of the neurotoxins from the venom of the scorpion Androctonus australis Hector, upon crayfish neuromuscular junctions has shown that the toxin strongly associates with the nerve terminal to stimulate release of neurotransmitters. The biochemical approach has shown that the binding of scorpion toxin I to rat brain synaptosomes is accompanied by a decrease in their capacity to accumulate gamma-aminobutyric acid. The main effect of the toxin is to stimulate neurotransmitter release. The apparent dissociation constant of the toxin-receptor complex is 0.1-0.2 muM at 22 degrees C. The rate of dissociation is so slow that complex formation seems to be quasi-irreversible. The "quasi-irreversibility" has also been observed in electrophysiological experiments with the crayfish neuromuscular junction. Tetrodotoxin prevents scorpion toxin I action if it is incubated with synaptosomes or with crayfish neuromuscular junctions before scorpion toxin I application. Tetrodotoxin does not reverse scorpion toxin action if it is added to the preparation after scorpion toxin I. Prevention of scorpion toxin action by tetrodotoxin permits measurements of binding characteristics of this toxin to synaptosomes. The dissociation constant of the tetrodotoxin-receptor complex is 2.2 nM at 22 degrees C. No cooperativity is observed in the binding. Because of its high affinity for synaptosomes (and the "quasi-irreversibility" of the binding), scorpion toxin I appears to be a potentially excellent tool for further studies of the molecular mechanism of neurotransmitter secretion.
Scorpion envenomation is quite common in India, southeast Asia, the U.S. southwest, and Israel (in the Negev and around Jerusalem). Yellow scorpion is considered the most dangerous scorpion that causes cardiac toxicity. Two patients are described, who lived in a nonendemic area of yellow scorpions and were envenomated by the black scorpion. Both suffered temporary cardiac involvement (manifested by electrocardiographic changes) which reverted to a normal pattern within 24 h. These are the first two cases that have been reported (from black scorpion envenomation) and indicate that the toxin of the black scorpion is also cardiotoxic, but much less than the "yellow scorpion" toxin.
A new anti-insect neurotoxin, AaH IT4, has been isolated from the venom of the North African scorpion Androctonus australis Hector. This polypeptide has a toxic effect on insects and mammals and is capable of competing with anti-insect scorpion toxins for binding to the sodium channel of insects; it also modulates the binding of alpha-type and beta-type anti-mammal scorpion toxins to the mammal sodium channel. This is the first report of a scorpion toxin able to exhibit these three kinds of activity. The molecule is composed of 65 amino acid residues and lacks methionine and, more unexpectedly, proline, which until now has been considered to play a role in the folded structure of all scorpion neurotoxins. The primary structure showed a poor homology with the sequences of other scorpion toxins; however, it had features in common with beta-type toxins. In fact, radioimmunoassays using antibodies directed to scorpion toxins representative of the main structural groups showed that there is a recognition of AaH IT4 via anti-beta-type toxin antibodies only. A circular dichroism study revealed a low content of regular secondary structures, particularly in beta-sheet structures, when compared to other scorpion toxins. This protein might be the first member of a new class of toxins to have ancestral structural features and a wide toxic range.