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Neutralization of Latrodectus mactans and L-hesperus venom by redback spider (L-hasseltii) antivenom
Abstract
Objective: To test the effectiveness of L. hasseltii (redback spider) antivenom in neutralizing the lethal effects oft. hesperus and L. mactans (North American black widow) venoms. Methods: LD50 values for the L. hesperus and L. mactans venom preparations were determined. A prospective, randomized, double-blind antivenom efficacy experiment was then performed for each venom using a mouse envenomation model. The following treatments were premixed and incubated at 25 degreesC for 1 hour prior to intraperitoneal injection: 1) saline control + protein control, 2) saline control + L. hasseltii antivenom, 3) L. hesperus or L. mactans venom + protein control, and 4) L. hesperus or L. mactans venom + L. hasseltii antivenom. The study endpoints were time elapsed until death and survival at 24 hours. Results. The mouse LD50 values for L. hesperus and L. mactans venoms were 0.64 mg/kg and 0.26 mg/kg, respectively. In the efficacy trial, all mice in group 3 (L. hesperus or L. mactans venom and protein control) died. In both experiments, all mice in group 4 (L. hesperus or L. mactans venom + antivenom) survived (p < 0.0001). Conclusion: This is the first study to derive mouse LD50 values for L. hesperus and L. mactans venom obtained by electrical stimulation of live adult spiders. Redback spider antivenom is effective in neutralizing the lethal effects of L hesperus and L. mactans venoms in a mouse envenomation model. While this study is limited by the optimized premixing of antigen with antibody, it generates the hypothesis that redback antivenom would be effective in the treatment of lactrodectism in humans caused by the two clinically relevant species of North American widow spiders.
... A number of in vitro studies have demonstrated that redback spider antivenom is able to neutralize the effects of the venom. [20][21][22] In addition, Graudins et al 21 showed that redback spider antivenom was able to prevent in vitro neurotoxicity in a chick isolated biventer cervicis nerve-muscle preparation and lethality in mice, from a range of widow spider venoms. Daly et al 22 also showed that redback spider antivenom prevented the lethal effects of L hesperus and L mactans. ...
... [20][21][22] In addition, Graudins et al 21 showed that redback spider antivenom was able to prevent in vitro neurotoxicity in a chick isolated biventer cervicis nerve-muscle preparation and lethality in mice, from a range of widow spider venoms. Daly et al 22 also showed that redback spider antivenom prevented the lethal effects of L hesperus and L mactans. It is therefore highly unlikely that poor clinical effectiveness in our study is due to the antivenom having poor binding or neutralization properties. ...
... 24 In addition, animal studies have demonstrated cross-neutralization of black widow spider venoms by redback spider antivenom. 21,22 The study therefore provides some support for the idea that widow spider antivenom may not be effective. The only other placebocontrolled randomized trial of widow spider antivenom also had negative results. ...
Study objective
Latrodectism is the most important spider envenomation syndrome worldwide. There remains considerable controversy over antivenom treatment. We aimed to investigate whether antivenom resulted in resolution of pain and systemic effects in patients with latrodectism who received standardized analgesia.
Methods
In a multicenter randomized placebo-controlled trial of redback spider antivenom for latrodectism, 224 patients (>7 years) with a redback spider bite and severe pain, with or without systemic effects, were randomized to receive normal saline solution (placebo) or antivenom after receiving standardized analgesia. The primary outcome was a clinically significant reduction in pain 2 hours after trial medication compared with baseline. A second primary outcome for the subgroup with systemic features of envenomation was resolution of systemic features at 2 hours. Secondary outcomes were improved pain at 4 and 24 hours, resolution of systemic features at 4 hours, administration of opioid analgesics or unblinded antivenom after 2 hours, and adverse reactions.
Results
Two hours after treatment, 26 of 112 patients (23%) from the placebo arm had a clinically significant improvement in pain versus 38 of 112 (34%) from the antivenom arm (difference in favor of antivenom 10.7%; 95% confidence interval −1.1% to 22.6%; P=.10). Systemic effects resolved after 2 hours in 9 of 41 patients (22%) in the placebo arm and 9 of 35 (26%) in the antivenom arm (difference 3.8%; 95% confidence interval −15% to 23%; P=.79). There was no significant difference in any secondary outcome between antivenom and placebo. Acute systemic hypersensitivity reactions occurred in 4 of 112 patients (3.6%) receiving antivenom.
Conclusion
The addition of antivenom to standardized analgesia in patients with latrodectism did not significantly improve pain or systemic effects.
... Latrodectus antivenom therapy is indicated for patients manifesting severe regional or systemic latrodectism, or for uncontrolled hypertension, seizures, or respiratory arrest. [21][22][23][24][25][26][27] Antivenom, 1−3 vials, diluted in 100−250 mL of 0.45% sodium chloride should be infused intravenously over a 1−2hour period. [21][22][23]26,27 Unrefined Latrodectus antivenom is often produced in horses exposed to Latrodectus bites, and has been associated with serum sickness, anaphylaxis (0.5% in an Australian series 10 ), and death. ...
... [21][22][23][24][25][26][27] Antivenom, 1−3 vials, diluted in 100−250 mL of 0.45% sodium chloride should be infused intravenously over a 1−2hour period. [21][22][23]26,27 Unrefined Latrodectus antivenom is often produced in horses exposed to Latrodectus bites, and has been associated with serum sickness, anaphylaxis (0.5% in an Australian series 10 ), and death. 21,23,26,27 Purified, Fabfragment Latrodectus antivenoms are now readily available in Australia and South America, and rarely cause severe immunologic complications, although serum sickness remains possible. ...
... [21][22][23]26,27 Unrefined Latrodectus antivenom is often produced in horses exposed to Latrodectus bites, and has been associated with serum sickness, anaphylaxis (0.5% in an Australian series 10 ), and death. 21,23,26,27 Purified, Fabfragment Latrodectus antivenoms are now readily available in Australia and South America, and rarely cause severe immunologic complications, although serum sickness remains possible. [21][22][23][25][26][27] In a retrospective analysis of all antivenom use in Australia over a one-year period, Sutherland reported that redback spider (L. ...
Spiders are carnivorous arthropods that coexist with humans and ambush or ensnare prey. Unlike other arthropods, spiders rarely transmit communicable diseases, and play a critical role in the ecosystem by consuming other arthropods that frequently transmit human diseases, such as mosquitoes and flies. There are more than 30,000 species of spiders, most of which are venomous, but they cannot inflict serious bites due to delicate mouthparts and short fangs. The differential diagnosis of spider bites is extensive and includes other arthropod bites, skin infections, and exposure to chemical or physical agents. However, approximately 200 species from 20 genera of spiders worldwide can cause severe human envenomings, with dermonecrosis, systemic toxicity, and death. Spider bites can usually be prevented by simple personal and domestic measures. Early species identification and specific management may help prevent serious sequelae of spider bites.
... The lack of stop codons, limited variability, conserved cysteine residues, similar lengths, and posttranslational processing signals of Latrodectus a-latrotoxin sequences, suggest that all species in the genus express a form of this vertebratespecific toxin with strong functional similarity to the ortholog from L. tredecimguttatus. This finding has important implications for treating widow spider bites globally (Graudins et al. 2002(Graudins et al. , 2012Daly et al. 2007). Black widow spiders are one of the two most clinically significant types of spiders worldwide (Vetter and Isbister 2008), with at least 5,000 envenomations reported annually in Australia for the red-back spider alone (Isbister and White 2004). ...
... Black widow spiders are one of the two most clinically significant types of spiders worldwide (Vetter and Isbister 2008), with at least 5,000 envenomations reported annually in Australia for the red-back spider alone (Isbister and White 2004). The limited sequence variability of a-latrotoxin across the mactans clade of Latrodectus (maximum pairwise nucleotide distance = 5.8%), explains why redback spider antivenom (RBSAV) is broadly effective in treating bites from other Latrodectus species (Daly et al. 2007;Graudins et al. 2012). ...
Black widow spiders (members of the genus Latrodectus) are widely feared because of their potent neurotoxic venom. α-Latrotoxin is the vertebrate-specific toxin responsible for
the dramatic effects of black widow envenomation. The evolution of this toxin is enigmatic because only two α-latrotoxin sequences
are known. In this study, ∼4 kb α-latrotoxin sequences and their homologs were characterized from a diversity of Latrodectus species, and representatives of Steatoda and Parasteatoda, establishing the wide distribution of latrotoxins across the mega-diverse spider family Theridiidae. Across black widow
species, α-latrotoxin shows ≥94% nucleotide identity and variability consistent with purifying selection. Multiple codon and
branch-specific estimates of the nonsynonymous/synonymous substitution rate ratio also suggest a long history of purifying
selection has acted on α-latrotoxin across Latrodectus and Steatoda. However, α-latrotoxin is highly divergent in amino acid sequence between these genera, with 68.7% of protein differences
involving non-conservative substitutions, evidence for positive selection on its physiochemical properties and particular
codons, and an elevated rate of nonsynonymous substitutions along α-latrotoxin’s Latrodectus branch. Such variation likely explains the efficacy of red-back spider, L. hasselti, antivenom in treating bites from other Latrodectus species, and the weaker neurotoxic symptoms associated with Steatoda and Parasteatoda bites. Long-term purifying selection on α-latrotoxin indicates its functional importance in black widow venom, even though
vertebrates are a small fraction of their diet. The greater differences between Latrodectus and Steatoda α-latrotoxin, and their relationships to invertebrate-specific latrotoxins, suggest a shift in α-latrotoxin toward increased
vertebrate toxicity coincident with the evolution of widow spiders.
... Latrodectus species are believed to contain similar a-LTX-like proteins since envenomation by any widow spider results in a similar clinical syndrome. Moreover, widow-spider antivenoms, produced using the venoms of specific Latrodectus species, reverse the effects of envenomation from other Latrodectus and Steatoda spiders (another member of the family Theridiidae) both in experimental animal models and in clinical settings32333435. The presence of a 130-kDa band in the venom of many theridiid spiders, detected by immunoblotting with red-back spider antivenom, suggests the presence of a-LTX-like or antigenically similar proteins in the venoms of all Latrodectus species as well as the related theridiid spider Steatoda grossa [32]. ...
... These findings therefore provide strong support for the widely held assumption that the clinical symptoms of latrodectism are due to the presence of a-LTX homologs in all theridiid venoms. The in vitro, in vivo and clinical observations of the effectiveness of red-back spider antivenom in the treatment of latrodectism from a wide range of Latrodectus species32333435 suggests that it may therefore be possible to use a single antivenom worldwide for the treatment of widow-spider envenomation. This is likely to impact less on regions that already have their own antivenom to treat envenomation by local Latrodectus species [56], but could potentially benefit many regions of the world where specific antivenoms to local widow spiders are not available. ...
The venom of the European black widow spider Latrodectus tredecimguttatus (Theridiidae) contains several high molecular mass (110-140 kDa) neurotoxins that induce neurotransmitter exocytosis. These include a vertebrate-specific α-latrotoxin (α-LTX-Lt1a) responsible for the clinical symptoms of latrodectism and numerous insect-specific latroinsectoxins (LITs). In contrast, little is known about the expression of these toxins in other Latrodectus species despite the fact that envenomation by these spiders induces a similar clinical syndrome. Here we report highly conserved α-LTX, α-LIT and δ-LIT sequence tags in Latrodectus mactans, Latrodectus hesperus and Latrodectus hasselti venoms using tandem mass spectrometry, following bioassay-guided separation of venoms by liquid chromatography. Despite this sequence similarity, we show that the anti-α-LTX monoclonal antibody 4C4.1, raised against α-LTX-Lt1a, fails to neutralize the neurotoxicity of all other Latrodectus venoms tested in an isolated chick biventer cervicis nerve-muscle bioassay. This suggests that there are important structural differences between α-LTXs in theridiid spider venoms. We therefore cloned and sequenced the α-LTX from the Australian red-back spider L. hasselti (α-LTX-Lh1a). The deduced amino acid sequence of the mature α-LTX-Lh1a comprises 1180 residues (∼132kDa) with ∼93% sequence identity with α-LTX-Lt1a. α-LTX-Lh1a is composed of an N-terminal domain and a central region containing 22 ankyrin-like repeats. The presence of two furin cleavage sites, conserved with α-LTX-Lt1a, indicates that α-LTX-Lh1a is derived from the proteolytic cleavage of an N-terminal signal peptide and C-terminal propeptide region. However, we show that α-LTX-Lh1a has key substitutions in the 4C4.1 epitope that explains the lack of binding of the monoclonal antibody.
... Analysis of the venoms of many Latrodectus species shows that the genetic sequences are highly conserved among the black widow taxa (Garb and Hayashi 2013). Because of this venom similarity, antivenom developed for the Australian redback counteracted the lethal effect of venoms of two American black widow (Daly et al. 2007). However, α-latrotoxin is less well genetically conserved in the brown widow clade of species (Garb and Hayashi 2013), which may explain why brown widow bites are not nearly as dynamic as that of the species in the black widow clade (Müller 1993). ...
... Analysis of the venoms of many Latrodectus species shows that the genetic sequences are highly conserved among the black widow taxa (Garb and Hayashi 2013). Because of this venom similarity, antivenom developed for the Australian redback counteracted the lethal effect of venoms of two American black widow (Daly et al. 2007). However, α-latrotoxin is less well genetically conserved in the brown widow clade of species (Garb and Hayashi 2013), which may explain why brown widow bites are not nearly as dynamic as that of the species in the black widow clade (Müller 1993). ...
... These trials suggest that acute allergic-type reactions occur in about 5% of cases, including anaphylaxis in 1–2% and delayed reactions or serum sickness in up to 10% of cases[4,[27][28][29]. The efficacy of widow-spider antivenom has been confirmed in the laboratory by Graudins et al.[30]for red-back spider antivenom and for L. hesperus and L. mactans venoms in a mouse envenomation model by Daly et al.[31]. ...
Latrodectism or envenomation by widow-spiders is common and clinically significant worldwide. Alpha-latrotoxin is the mammalian-specific toxin in the venom that results in toxic effects observed in humans. Symptoms may be incapacitating and include severe pain that can persist for days. The management of mild to moderate latrodectism is primarily supportive while severe cases have variously been treated with intravenous calcium, muscle relaxants, widow-spider antivenom and analgesic opioids. The object of this systematic review is to examine the literature on the clinical effectiveness of past and current treatments for latrodectism. MEDLINE, EMBASE and Google Scholar were searched from 1946 to December 2016 to identify clinical studies on the treatment of latrodectism. Studies older than 40 years and not in English were not reviewed. There were only two full-publications and one abstract of placebo-controlled randomised trials on antivenom use for latrodectism. Another two randomised comparative trials compared the route of administration of antivenom for latrodectism. There were fourteen case series (including two abstracts), fourteen case reports and one letter investigating drug treatments for latrodectism with the majority of these also including antivenom for severe latrodectism. Antivenom with opioid analgesia is often the major treatment reported for latrodectism however; recent high quality evidence has cast doubt on the clinical effectiveness of this combination and suggests that other treatments need to be investigated.
... The cross neutralization provided by different anti-Latrodectus antivenoms has been previously described. Some examples are those of the cross neutralization between antivenoms against L. halsetti from Australia on L. mactans and L. hesperus from North America (Daly et al., 2001) and that of anti-L. tredecimguttatus from Europe and Asia on venom of L. mactans from North America (Keegan, 1955). ...
“Black widow” spiders belong to the genus Latrodectus and are one of the few spiders in the world whose bite can cause severe envenomation in humans and domestic animals. In Argentina, these spiders are distributed throughout the country and are responsible for the highest number of bites by spiders of toxicological sanitary interest. Here, we studied the toxicity and some biochemical and immunochemical characteristics of eighteen venom samples from Latrodectus spiders from eight different provinces of Argentina, and the neutralization of some of these samples by two therapeutic antivenoms used in the country for the treatment of envenomation and by a anti-Latrodectus antivenom prepared against the venom of Latrodectus mactans from Mexico. We observed important toxicity in all the samples studied and a variation in the toxicity of samples, even in those from the same region and province and even in the same Latrodectus species from the same region. The therapeutic antivenoms efficiently neutralized all the venoms studied.
... Most countries, however, do not have Latrodectus antivenom available. Latrodectism from one species may be effectively treated by antivenom raised against a different species [38,39]. This observation is likely due to preservation of the antigenetically similar latrotoxin molecules across the genus. ...
Black widow spider (Latrodectus mactans) envenomation has been recognized since antiquity. The syndrome, latrodectism, is characterized by painful muscle rigidity and autonomic disturbances such as tachycardia, hypertension, and diaphoresis. Symptoms typically last for 1-3 days. Treatment has ranged from local folk remedies to administration of specific antivenom. Opioid analgesics combined with muscle relaxants, such as benzodiazepines, are only effective at symptomatic and temporary control. Antivenom is by far the most efficacious therapy available based on symptom resolution, need for subsequent therapy, and hospital admission rates. Fear of allergic type reactions from antivenom administration has limited its use in the United States. A new purified F(ab)2 fragment Latrodectus mactans antivenom, Analatro®, is currently undergoing clinical trials. The product is expected to have similar efficacy and be associated with fewer adverse reactions when compared to the currently available partially purified whole IgG Merck product. This shift in the risk-benefit analysis may ultimately lead to more antivenom administration in significantly envenomated patients.
Lizards and spiders are natural adversaries, yet little is known of adaptations that lizards might possess for dealing with the venomous defences of spider prey. In the Western USA, two lizard species (Elgaria multicarinata and Sceloporus occidentalis) are sympatric with and predate western black widow spiders (Latrodectus hesperus). The consequences of black widow spider venom (BWSV) can be severe, and are well understood for mammals but unknown for reptiles. We evaluated potential resistance to BWSV in the lizards that consume black widows, and a potentially susceptible species (Uta stansburiana) known as prey of widows. We investigated BWSV effects on whole-animal performance (sprint) and muscle tissue at two venom doses compared with control injections. Sprint speed was not significantly decreased in E. multicarinata or S. occidentalis in any treatment, while U. stansburiana suffered significant performance reductions in response to BWSV. Furthermore, E. multicarinata showed minimal tissue damage and immune response, while S. occidentalis and U. stansburiana exhibited increased muscle damage and immune system infiltration in response to BWSV. Our data suggest predator–prey relationships between lizards and spiders are complex, possibly leading to physiological and molecular adaptations that allow some lizards to tolerate or overcome the dangerous defences of their arachnid prey.
Despite the disrepute spiders have had for centuries, their bite is a rare occurrence. In the Mediterranean area, only two of the numerous known species are considered of medical significance: Latrodectus tredecimguttatus and Loxosceles rufescens. Spider bites have no pathognomonic signs or symptoms, therefore most diagnoses are presumptive; a spider bite can only be diagnosed when a spider (seen at the time of the bite) is collected and identified by an expert, since most physicians and patients are unable to recognize a certain spider species or distinguish spiders from other arthropods. Skin lesions of uncertain etiology are too often attributed to spider bites. In most cases, these are actually skin and soft-tissue infections, allergic reactions, dermatoses etc. Misdiagnosing a wound as a spider bite can lead to delays in appropriate care, cause adverse or even fatal outcomes and have medical-legal implications. Concerningly, misinformation on spider bites also affects the medical literature and it appears there is lack of awareness on current therapeutic indications for verified bites.
This is the first report of the large-scale experimentally production of an equine antivenom against redback spider (Latrodectus hasseltii) lived in Japan. We captured 10,000 redback spiders in Japan and prepared the toxoids of crude venom extract, mixed the toxoids with mineral oil adjuvant, and immunized repeatedly it to healthy horses over a period of several weeks. Then, we separated the horse plasma, and purified the γ-globulin fraction and stocked as a purified antivenom concentrate. Consequently, we manufactured approximately 6,500 vials of a single-dose freeze-dried test lot from a portion of the purified γ-globulin fraction, equivalent to the extract derived from 520 spiders. This test lot had an antitoxin titer comparable to that of a similar drug commercially available overseas (liquid preparation), and the other quality met all reference specifications pre-specified based on the Minimum Requirements for Biological Products and other guidelines relevant for existing antivenom drug products in Japan.
Blood serum from immunized humans or animals (e.g., horses) contains relevant antibodies and has been used as serum therapy to treat many diseases or envenomation events. The effectiveness of blood serum was initially discovered in 1890 when Kitasato and von Behring observed the effectiveness of this type of therapy against diphtheria and tetanus. Serum therapies played an important role in the advancement of modern medicine prior to the development of penicillin and steroids. At present, several types of serum therapy remain in clinical use. However, some physicians have a limited understanding of the nature and the benefits of serum therapy and the factors that require particular attention. In this review, we set out to clarify the benefits, cautions, and potential applications of serum therapy in the context of conditions such as gas gangrene, diphtheria, botulism, and tetanus and bites from three snake species (mamushi, habu, and yamakagashi) and the redback spider. It is hoped that this review will help clinicians to learn about clinical serum therapies and become familiar with their applications.
Class InsectaClass ArachnidaClass Chilopoda (centipedes) and Diplopoda (millipedes)Other noxious or venomous invertebratesNoxious or venomous vertebratesOther animal bites
This chapter describes the administration of specific immunoglobulin antibodies or antibody fragments (IgG, Fab, F(ab′)2, or sFv) to treat toxic exposures. Binding of the antibody to the target molecules or antigen [1] is intended to result in partial or complete neutralization of the toxic effect of the target, a concentration gradient of free target molecules encouraging efflux into the vascular compartment, and ultimate elimination of the antibody/target complex by renal or reticuloendothelial system routes [2–4].
Widow spiders (Latrodectus spp.), also known as "black widows", have a worldwide distribution and can cause latrodectism. To the best of our knowledge, in Brazil, only one case of Latrodectus geometricus (Koch, 1841) envenomation in a human has been reported. The aim of the present report is to describe a spider bite caused by Latrodectus geometricus in a patient who lives in Paranapanema, São Paulo state, Brazil.
Study objective:
Black widow spider antivenom has never been tested in a randomized clinical trial, to our knowledge. We explore various efficacy measures for a novel F(ab)2 antivenom in patients with moderate to severe pain caused by black widow spider envenomation.
Methods:
A randomized, placebo-controlled, double-blind, clinical trial was conducted in 12 academic emergency departments. We included patients at least 10 years old with moderate to severe latrodectism. Subjects received either a single intravenous infusion of antivenom or placebo. Pain was assessed with the visual analog scale. The primary efficacy outcome was the difference in pre- and posttreatment visual analog scale score. Prospectively defined secondary outcomes included treatment failures and time to clinically important decrease in pain.
Results:
Twenty-four subjects were enrolled between October 2005 and October 2006; 13 were randomized to antivenom and 11 to placebo. The median change in visual analog scale at 150 minutes posttreatment was -50.0 mm (Interquartile Range [IQR] -67, -41 mm) in the antivenom treatment group and -46.0 mm (IQR -51, 0 mm) in the placebo treatment group (P=.14). There were 7 treatment failures (64%; 95% confidence interval 35% to 92%) in the placebo group and 3 (23%; 95% confidence interval 0.2% to 46%) in the antivenom group (P=.06). The median time to a clinically important decrease in pain after treatment was shorter in the antivenom group compared with the placebo group (30 minutes [IQR 30, 60 minutes] versus 90 minutes [IQR 30, 90 minutes]; P=.03). No serious adverse events or deaths were reported.
Conclusion:
Although the overall reduction in pain was similar for antivenom- and placebo-treated subjects, antivenom reduced pain more rapidly than placebo. No significant adverse events occurred in either group.
There are several groups of medically important araneomorph and mygalomorph spiders responsible for serious systemic envenomation. These include spiders from the genus Latrodectus (family Theridiidae), Phoneutria (family Ctenidae) and the subfamily Atracinae (genera Atrax and Hadronyche); The venom of these spiders contains potent neurotoxins that cause excessive neurotransmitter release via vesicle exocytosis or modulation of voltage-gated sodium channels.-In addition, spiders of the genus Loxosceles (family Loxoscelidae) are responsible for significant local reactions resulting in necrotic cutaneous lesions. This results from sphingomyelinase D activity and possibly other compounds. A number of antivenoms are currently available to treat envenomation resulting from the bite of these spiders. Particularly efficacious antivenoms are available for Latrodectus and Atrax/Hadronyche species, with extensive cross-reactivity within each genera. In the case of Latrodectus antivenoms this is of considerable importance in countries where antivenom is unavailable or where certain antivenoms are associated with an unacceptably high risk,of adverse reactions. Moreover, Latrodectus and Atrax antivenoms appear, to be effective in the treatment of envenomation by closely related Steatoda spiders (family Theridiidae) or the unrelated spider Missulena bradleyi (family Actinopodidae), respectively., The effectiveness of Loxosceles antivenom in the treatment of the necrotic arachnidism resulting from the bite of recluse spiders is less clear mainly due to late presentation of victims. Antivenom is also available for Phoneutria envenomation but is reserved only for severe cases.
Following widow spider (Latrodectus sp.) envenomation, local pain, erythema, abdominal pain, rigidity, hypertension, and diaphoresis can be seen. While an effective specific antivenom (AV) is available, its use is limited due to concern of possible severe allergic reaction. We performed the current study to determine rate of adverse effects and the efficacy of AV in patients treated for widow spider envenomation.
Observational case series of the California Poison Control System electronic database from January 1999 to December 2009. All cases of widow spider envenomation treated with AV were included. Age, gender, signs, and symptoms, adjunctive therapy, number of vials of AV given, and adverse reaction to AV were recorded. Descriptive statistical methods were used.
Ninety-six patients received AV, mean age 26 years (0.12-74 years), 76% male. Following widow spider envenomation generalized pain was reported in 91%, erythema at site in 57%, hypertension (≥ 140/90 mmHg) in 43%, muscle rigidity/cramping in 43%, abdominal pain in 41%, tachycardia (≥ 100 bpm) in 23% and diaphoresis in 21%. No patient required more than one vial of AV. One patient developed urticaria to AV halfway through infusion which was immediately discontinued. Another patient developed generalized flushing following completion of infusion but had no other effects. Two other patients reported myalgia and paresthesia. There were no deaths in any patients receiving AV. There was no shortness of breath or respiratory distress, no hypotension or chest pain following AV administration. All patients reported pain relief with AV and did not require additional AV doses.
Our results suggest that Black Widow Spider Antivenin® (Merck) administration is relatively safe with mild to moderate adverse effects seen in only a small percentage of patients. There were no deaths, or severe allergic reactions identified. The retrospective use of poison control system data is a limitation of our study. Further prospective studies are needed to validate our findings and elucidate the full safety profile on this antivenom.
Black widow spider (Latrodectus spp.) envenomation remains the most clinically significant spider envenomation in the US. The syndrome is characterized by painful muscle rigidity and autonomic disturbances. Treatment has ranged from symptomatic care to administration of specific antivenom. Declining antivenom availability and, possibly, the fear of hypersensitivity allergic reactions, has limited antivenom use in the US.
To describe Latrodectus spp. exposures and the subsequent treatment reported to US poison centers; the secondary objective was to identify factors associated with shorter duration of symptoms (<24 hours).
All Latrodectus spp. exposures reported to the National Poison Data System (NPDS) between January 1, 2000, and December 31, 2008, were reviewed. Cases with at least minor clinical effects due to Latrodectus spp. exposure were extracted. Descriptive statistics were generated. The probability that symptom duration was less than 24 hours was modeled, using logistic regression.
From 2000 through 2008, a total of 23,409 Latrodectus spp. exposures were reported in 47 states; 9872 cases had at least minor clinical effects and were included in the subsequent analysis. Exposures peaked in September and fell to a nadir in January and February. Fifty-eight percent of the cases involved males, and the mean (SD) age was 31.5 (17.4) years. Sixty-five percent of the patients had minor clinical effects, 33.5% had moderate effects, 1.4% had major effects, and there were no deaths. Antivenom use was associated with symptom duration of less than 24 hours in moderate and major outcome groups. There was no evidence of shorter symptom duration in patients who received benzodiazepines or calcium. Adverse drug reactions were more common in patients receiving benzodiazepines and antivenom.
In the US, most symptomatic Latrodectus spp. exposures reported to the NPDS are minor. Few patients receive antivenom, although antivenom is associated with shorter symptom duration among moderate and major outcomes.
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.
The family Theridiidae (comb-footed spiders) contains the well-known and medically important widow spider group (Latrodectus spp.). Little is known about the effects of envenoming by other common members of this family.
The objective of this study was to determine the clinical effects of bites by common theridiid spiders of the genera Steatoda and Achaearanea.
This was a prospective cohort study of calls to Australian poison information centers and presentations to emergency departments. Twenty-eight persons with a definite bite by a spider of the family Theridiidae, excluding Latrodectus spp., were included where the spider was immediately collected and expertly identified from February 1999 to April 2002.
There were 23 bites by Steatoda spp. and five bites by Achaearanea spp. Steatoda bites occurred across Australia, throughout the year, and the majority during waking hours. Seventy-eight percent of bites occurred indoors and 48% while dressing indoors. Pain was universal and was severe in six (26%). Increasing pain in the first hour occurred in 30%, and the median duration of pain was 6 hr (interquartile range: 1-12 hr). Local or regional diaphoresis did not occur. Systemic effects occurred in 30% and included nausea, headache, lethargy, and malaise. The majority received no treatment: seven patients presented to a hospital (two patients received opiates for analgesia) and 1 patient inadvertently received intravenous redback spider (RBS) antivenom because the spider was initially misidentified as a RBS (Latrodectus). The pain and symptoms responded over 1 hr following antivenom administration. Bites by Achaeranea spp. caused moderate to severe persistent pain, but no systemic effects.
Steatoda spp. bites or "steatodism" may cause prolonged pain and systemic effects similar to Latrodectus bites, but less severe. In severe cases, the clinical effects were almost indistinguishable from Latrodectus, except diaphoresis was absent, and the spiders were often mistaken for Latrodectus. Intravenous RBS antivenom appears to be an effective treatment in isolated severe cases, consistent with in vitro work. Achaearanea bites caused pain similar to Latrodectus bites.
The venoms used in this study were lyophilized homogenates of venom glands taken from mature female Latrodectus mactans mactans, L. variolus, L. bishopi and L. geometricus. Qualitative neutralization tests showed that 0.25 ml of the commercial antivenin “Lyovac” protected mice from the lethal effects of a minimum of 5 LD50 of each of the venoms. Micro double-diffusion tests, using “Lyovac”, were carried out on agar covered microscope slides. The venoms of L. mactans mactans and L. variolus formed 8 precipitation lines, while those of L. bishopi and L. geometricus formed 7 and 5 lines respectively. The venom proteins of each of the venoms were fractionated by disc electrophoresis. Eight major fractions were separated from L. mactans mactans, L. variolus and L. bishopi venom and 6 from the venom of L. geometricus. Each venom had a distinct electrophoretic pattern.
To review cases of black widow spider envenomation to describe the clinical presentation and evaluate the efficacy of treatment.
Retrospective chart review.
An urban toxicology referral center.
All patients attended by the toxicology service and discharged from our hospital between January 1982 and December 1990 with a diagnosis of black widow spider envenomation.
Inclusion criteria were either a positive black widow spider identification or a visible envenomation site ("target lesion"). Depending on the clinical presentation, patients were categorized as grade 1, 2, or 3 in severity. The efficacy and side effects of treatment alternative were evaluated.
One hundred sixty-three patients met the inclusion criteria. The most common sites of envenomation were the upper and lower extremities. The most common presenting complaint was generalized abdominal, back, and leg pain. One hundred eighteen patients initially presented to our institution, and 45 were transfers. Pain relief of grade 2 and 3 envenomations was achieved most effectively with either black widow spider-specific antivenin alone or a combination of IV opioids and muscle relaxants. Fifty-eight patients received antivenin with complete resolution of symptoms in a mean time of 31 +/- 26.7 minutes. Of the 118 patients initially seen at our institution, the mean total duration of symptoms was 9 +/- 22.7 hours in patients receiving antivenin and 22 +/- 24.9 hours in patients not receiving antivenin. Fifty-two percent of patients not receiving antivenin required hospitalization, whereas only 12% of those receiving antivenin were admitted. One patient died of severe bronchospasm after receiving antivenin. Calcium gluconate was not effective in providing symptomatic relief in this series, with 96% of the grade 2 and 3 envenomations treated initially with calcium gluconate requiring the addition of IV opioids or other analgesics for symptomatic relief. Fifty-five percent of patients initially receiving IV morphine and 70% of those initially receiving both IV morphine and benzodiazepines obtained symptomatic relief without additional medication.
One hundred sixty-three envenomations by black widow spiders were reviewed and graded according to severity with treatment modalities evaluated. Although calcium gluconate usually has been considered the first-line treatment of severe envenomations by black widow spiders, we found it ineffective for pain relief compared with a combination of IV opioids and benzodiazepines. The use of antivenin significantly shortened the duration of symptoms in severe envenomations.
A method is described for the assessment of lethal toxicity of venoms using a modified LD50 assay. With this test it is possible to obtain an LD50 using only 8-10 experimental animals, instead of 30 or more. It is suggested for ethical, scientific and economic reasons that this method be tested in laboratories involved in screening of venoms for lethality and, if found satisfactory, it should replace the classical LD50 assay.
Because there are few recent studies of black widow spider (Latrodectus Mactans) envenomation, a six-year retrospective study was conducted by patients admitted to or discharged from our hospital with this diagnosis. Fourteen patients with apparently severe envenomation were found and reviewed for the frequency of presenting signs and symptoms, the use of laboratory and radiographic studies, and the effectiveness of drug therapies. The most frequent symptoms were bite site pain (79%), abdominal pain (71%), and lower extremity weakness (57%). The most frequent signs were bite site lesions and abdominal tenderness or rigidity (71%). Laboratory and radiographic studies did not influence the initial emergency department evaluation. All drug therapies resulted in good clinical outcome despite two complications, and we therefore believe that the use of antivenom for symptomatic relief should be discouraged.
The objective of this study was to review widow spider envenomation on a worldwide basis, with an emphasis on regional variability in management, particularly between the United States and Australia. Data sources were the Medline database (1966-1997) for English language references using as key words widow spider, latrodectism, and red back spider, and Mesh headings. Textbooks of toxinology were also used. Studies involving clinical reports and series were selected. The data indicated that envenomation by widow spiders (latrodectism) is common worldwide. Local pain and sweating predominate, in about 25% of cases becoming generalized or developing in remote sites. The mortality in published series varies from 5% to 10%, although these may be overestimates. Australia may have the highest rate of latrodectism in the world. The literature reveals regional disparities in the treatment and outcome of latrodectism. In Australia, intramuscular antivenin has been used liberally for more than 40 years with a very low rate (0.5% to 0.8%) of allergic reactions and no deaths recorded since its introduction. Antivenin is routinely successful in relieving the effects of latrodectism. In the United States, the antivenin is given intravenously, is usually reserved for very severe cases, and the rate of allergic reaction is high (from 9% up to 80% in those skin testing positive). Deaths have been recorded after antivenin. The literature suggests that antivenin to one species of Latrodectus is likely to be effective against other species. The conclusion drawn was that latrodectism is a common envenomation worldwide. There is a strong case for a comparative trial of Australian vs US antivenin in treating latrodectism due to the black widow spider in the United States.
Four species of the black-widow spider genus Latrodectus are known to occur in North America. They are L. mactans mactans, L. geometricus, L. variolus and L. bishopi. Thecomparative lethality of the venoms of these species and of the European sub-species L. mactans tredecimguttatus was evaluated. All have very potent venoms although there are species differences in venom lethality and the average amount of venom obtained.