Scorpion Envenomation Research Articles

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Spatial Distribution of Medically Important Scorpions in Iran: A Review Article

Context: There are three families and 66 species of scorpions in Iran, some of these species are medically relevant, and their sting cause public health problems. Thus, producing of the new geographical distribution of scorpions and the new species is very important. The goal of this study was to produce the distribution maps of Iranian scorpions that are medically important according to the latest information. Evidence Acquisition: This present study included a review of all the articles related to Iranian scorpions published in ISI, PubMed, Scopus, ScienceDirect, and Google Scholar databases during 2008 - 2019, using the relevant MeSH keywords. The data were entered in an Excel file, and spatial distribution maps were prepared. Results: From the review of the related published documents, we found that there are 66 scorpion species in Iran, some scorpion names have been changed and new scorpion species have been added to Iranian scorpion fauna and the spatial distribution of some species has become wider. Conclusions: Considering the new distribution maps and data on Iranian scorpions, for scorpion envenomation treatment and control programs, these variations should be regarded.

Echocardiography versus cardiac biomarkers for myocardial dysfunction in children with scorpion envenomation: An observational study from tertiary care center in northern India.

ObjectiveThis study was done to evaluate myocardial function by 2D Echocardiography and Cardiac biomarkers (cTnI, CK-MB, BNP) changes in patients of scorpion envenomation of grade II-IV and correlate mortality of envenomed children with myocardial dysfunction. MethodsA total of 40 patients admitted consecutively with grade II and more scorpion envenomation from October 2015 to July2018 were enrolled in the study. The data included demographics, the time of presentation, clinical features, echocardiographic findings, electrocardiographic findings, cardiac biomarker levels at admission and discharge, use of inotropic medication, oral prazosin, time of discharge, and their outcome. ResultsThe most common ECG abnormality was sinus tachycardia 28 (70%) followed by low voltage complex 13 (32.5%) which got normalized at the time of discharge in majority. Cardiac troponin I (cTnI) levels were more than 0.1 ng/mL, suggesting myocarditis was present in 25 (62.5%) and got normalized at discharge. CK-MB levels were increased in 26 (65%) patients suggesting myocardial involvement. BNP levels were also increased in 24 (60%) patients suggesting heart failure and its value got normalized at discharge. Abnormal 2D Echo findings as reduced left ventricular ejection fraction (LVEF) was present in 18 (45%) cases suggesting myocardial dysfunction and became normal at discharge. The sensitivity, specificity, positive predictive value and negative predictive value of Cardiac troponin I (cTnI) considering ECHO cardiograph as gold standard were 100, 68.1, 72 and 100% respectively. One patient had died whose Ejection fraction was less than 30%. ConclusionEchocardiography and cTnI can identify subgroup of patients, who require early aggressive therapy. Echocardiography, if not available, cardiac troponin I level can guide early therapy and indicates the prognosis.

Epidemiological Characteristics of Scorpionism in West Azerbaijan Province, Northwest of Iran.

Background:There are four medically important scorpion species (Mesobuthus eupeus, Mesobuthus caucasicus, Androctonus crassicauda and Hottentotta saulcyi) in the West Azerbaijan Province, northwestern Iran. scorpionism is considered as a health problem in this region, because there is no information about scorpion envenomation, this study was designed to study epidemiological characteristics of scorpionism to optimize prevention and treatment of scorpion sting in northwest of Iran.Methods:All the data from epidemiological surveys completed in West Azerbaijan hospitals over four years (2014–2017) for scorpion victims were collected. This information includes the number of victims, sex, age, signs and symptoms, site of sting, body parts of victims, history of previous sting, the condition of the patient in terms of recovery and death, and the time to receive anti venom, all data were analyzed by the Excel software.Results:A total of 2718 cases of scorpionism were reported from March 2014 to March 2017 in the study area. The most cases occur in both sexes in the age groups of 25 to 34 years old. In urban areas 40.3% of people and in rural areas 59.7% of them have suffered. The Poldasht and Chaldoran cities, had the most and least incidence respectively.Conclusion:In this study, the high risk areas in the case of scorpion stings were identified. Results of this study can be used to design preventive programs to educate more people about dangerous areas to prevent scorpion sting and even death.

Tityus stigmurus venom causes genetic damage in blood and testicular cells and affects the number and morphology of gametogenic lineage cells in mice

Scorpion envenomation represents an important health problem in many parts of the world, due to the high number and severity of accidents. Recent studies demonstrated that some species can produce venoms with genetic damage potential. Here, we evaluated whether Tityus stigmurus venom causes genetic damage in blood and testicular cells of Swiss mice. We also analyzed the effect of the venom on the number of spermatogenic lineage cells. Five groups of mice received 0.387 mg/kg of the venom, intraperitoneally; one group received saline solution (control group). Blood and testicular cells were collected for comet assay and histological analysis at different times after treatment (1, 2, 6, 12, and 48 h). Blood was also collected 48 h after treatment for the micronucleus test in erythrocytes. Histological analysis was performed by counting cells of the spermatogenic lineages; the nuclear area of elongated spermatocytes was also evaluated. Treatment with the venom induced DNA damage that endured from 1 h to 48 h, as confirmed by the comet assay. The micronucleus test demonstrated that the venom induced mutations in erythrocytes. The number of spermatogonia and rounded spermatids decreased in some groups; the number of elongated spermatids increased, and their nuclear size decreased 1 h after treatment. Genetic damage can be caused directly by the venom, but we suggested that reactive oxygen species that result from inflammatory process caused by the envenomation may have an important role in the DNA damage. Genetic damage and apoptosis may explain the changes in the number of spermatogenic cells. Furthermore, the decrease in nuclear area may result from chromatin loss. Genetic damage in testicular cells, associated with alterations in the number and morphology of spermatogenic cells, can result in reproduction disorders in animals, or humans, stung by T. stigmurus.

Demographic and epidemiological characteristics of scorpion envenomation and daily forecasting of scorpion sting counts in Touggourt, Algeria.

OBJECTIVESThis study was conducted to provide better insights into the demographic and epidemiological characteristics of scorpion envenomation in an endemic area in Algeria and to identify the model that best predicted daily scorpion sting counts.METHODSDaily sting data from January 1, 2013 to August 31, 2016 were extracted from questionnaires designed to elicit information on scorpion stings from the two emergency medical service providers in Touggourt, Algeria. Count regression models were applied to the daily sting data.RESULTSA total of 4,712 scorpion sting cases were documented, of which 70% occurred in people aged between 10 years and 49 years. The male-to-female ratio was 1.3. The upper and lower limbs were the most common locations of scorpion stings (90.4% of cases). Most stings (92.8%) were mild. The percent of people stung inside dwellings was 68.8%. The hourly distribution of stings showed a peak between 10:00 a.m. and 11:00 a.m. The daily number of stings ranged from 0 to 24. The occurrence of stings was highest on Sundays. The incidence of scorpion stings increased sharply in the summer. The mean annual incidence rate was 542 cases per 100,000 inhabitants. The fitted count regression models showed that a negative binomial hurdle model was appropriate for forecasting daily stings in terms of temperature and relative humidity, and the fitted data agreed considerably with the actual data.CONCLUSIONSThis study showed that daily scorpion sting data provided meaningful insights; and the negative binomial Hurdle model was preferable for predicting daily scorpion sting counts.

Basal ganglia hemorrhage secondary to scorpion sting: a fatal presentation

IntroductionCerebrovascular manifestations are uncommon presentations of scorpion sting in the Indian subcontinent. Encephalopathy, cerebral edema, subarachnoid hemorrhage, non-hemorrhagic strokes, and cortical necrosis are a few CNS complications described in the medical literature due to scorpion envenomation.Case descriptionWe report a rare case of scorpion envenomation in a 40-year old, non-hypertensive farmer, who presented in an unconscious state. Non-contrast CT head revealed intracerebral hemorrhages in left temporoparietal lobe extending into left basal ganglia with intraventricular extension.Discussion and evaluationToxin-induced autonomic storm is mostly responsible for the acute hypertensive crisis in affected individuals leading to stroke (commonly cerebral infarct) as a CNS complication.ConclusionBasal ganglia bleed following scorpion sting is an extremely rare scenario which is usually fatal as was in our case. Early suspicion and prompt institution of treatment (prazosin) is crucial in the management of intracranial bleed secondary to scorpion sting.

Investigation of the Behavioral and Clinical Effects of Black Scorpion Venom in Albino Rats

Background: Aggressive behaviors in human and experimental animals have previously been described following induced pain. Aggression in rodents has been attributed to genetic and environmental factors, such as pain. A major complication of scorpion envenomation is severe pain in animals and humans. Considering that envenomation by black scorpion (Androctonus crassicauda) induces severe pain, the present study was conducted to investigate the effects of the venom on inducing aggressive behaviors in rats due to the pain from stinging. Methods: Rats in the control (n=20) and experimental groups (n=20) were injected with 0.5ml physiological serum or 1µg/ml of black scorpion venom dissolved in 0.5ml physiological serum, respectively, in the dorsal vein near the tail. Changes in behaviors were monitored photographically among the rats in both groups. Results: Following the injection of the scorpion venom, considerable agitation and fights occurred among the experimental rats, presumably due to the severe pain induced by the venom. However, there was no such abnormal behavior observed in the control rats and in the experimental rats before the venom injection. Conclusion: The induced pain post envenomation in rats caused violent changes in their behaviors, which were highly likely associated with the venom injection.

Severe acute myocarditis due to scorpion envenoming: unusual presentation in adults

Severe acute myocarditis due to scorpion envenoming: unusual presentation in adults

Snake, spider, scorpion, insect, and marine exposures and envenomations in pregnancy in the national poison data system, 2009–2018

Snake, spider, scorpion, insect, and marine exposures and envenomations in pregnancy in the national poison data system, 2009–2018

Neurotoxicity of Tityus bahiensis (brown scorpion) venom in sympathetic vas deferens preparations and neuronal cells

Systemic scorpion envenomation is characterized by massive neurotransmitter release from peripheral nerves mediated primarily by scorpion venoms neurotoxins. Tityus bahiensis is one of the medically most important species in Brazil, but its venom pharmacology, especially regarding to peripheral nervous system, is poorly understood. Here, we evaluated the T. bahiensis venom activity on autonomic (sympathetic) neurotransmission by using a variety of approaches, including vas deferens twitch-tension recordings, electrophysiological measurements (resting membrane potentials, spontaneous excitatory junctional potentials and whole-cell patch-clamp), calcium imaging and histomorphological analysis. Low concentrations of venom (≤ 3 μg/mL) facilitated the electrically stimulated vas deferens contractions without affecting postsynaptic receptors or damaging the smooth muscle cells. Transient TTX-sensitive sustained contractions and resting membrane depolarization were mediated mainly by massive spontaneous ATP release. High venom concentrations (≥ 10 μg/mL) blocked the muscle contractions and induced membrane depolarization. In neuronal cells (ND7-23wt), the venom increased the peak sodium current, modified the current-voltage relationship by left-shifting the Nav-channel activation curve, thereby facilitating the opening of these channels. The venom also caused a time-dependent increase in neuronal calcium influx. These results indicate that the sympathetic hyperstimulation observed in systemic envenomation is presynaptically driven, probably through the interaction of α- and β-toxins with neuronal sodium channels.

Involvement of the Endothelin Receptor Type A in the Cardiovascular Inflammatory Response Following Scorpion Envenomation.

Elevated levels of endothelin-1 (ET-1) were recorded in sera of scorpion sting patients. However, no studies focused on the mechanism of ET-1 involvement in the pathogenesis of scorpion envenomation, particularly in the cardiovascular system which is seriously affected in severe cases of scorpion stings. Inflammation induced by Androctonus australis hector (Aah) scorpion venom in the heart together with the aorta was studied in mice pretreated with a specific endothelin A receptor (ETA-R) inhibitor. ETA-R inhibition resulted in the attenuation of the high amounts of cytokine (tumor necrosis factor alpha (TNF-α) and interleukin-17 (IL-17)) recorded in the sera of envenomed mice. The recovery of the oxidative stress marker balance and matrix metalloproteinase (MMP) expression were also observed, concomitantly with the reduction of tissular neutrophil infiltration. Additionally, the cardiac and the aortic tissue alterations, and the metabolic enzymes (creatine kinase (CK) and muscle–brain isoform creatine kinase (CK-MB)) overspread into sera were significantly attenuated. Obtained results suggest the implication of endothelin throughout its ETA receptors in the inflammatory response observed in the cardiovascular components during scorpion envenomation. Further knowledge is needed to better understand the implication of the endothelin axis and to improve the therapeutic management of severe scorpion sting cases.

Complete neutralization of the lethality of Hemiscorpius lepturus crude venom by a novel anti-recombinant phospholipase D1 IgGs

Treatment of scorpion envenomation is a challenging issue since serotherapy is implemented by administration of polyvalent equine antisera. In our previous study we discovered that recombinant phospholipase D1 (Hl-RecPLD1) is responsible for the lethality of Hemiscorpius lepturus (H. lepturus) venom in mice. Accordingly, this study was aimed to investigate the protectivity of purified anti-Hl-RecPLD1 IgG against the lethality or major complications of H. lepturus venom. The neutralization efficiency of purified anti-Hl-RecPLD1 IgGs against sphingomyelinase activities of the crude venom and Hl-RecPLD1 was also assessed. Anti-Hl-RecPLD1 IgGs at optimum amount of 3.7 mg completely neutralized one Lethal Dose 100 (LD100) of crude venom in mice. The anti-Hl-RecPLD1 IgGs remarkably reduced the necrosis area from 6.5 to 1 cm2 in rabbit derma, induced by the crude venom. The anti-Hl-RecPLD1 IgGs remarkably reduced the sphingomyelinase and hemolytic activities of crude venom as well. In conclusion, a novel rabbit monovalent IgG against Hl-RecPLD1 was able to completely protect the mice against the lethality of H. lepturus crude venom and reduced its toxicity as well. Such monovalent anti-Hl-RecPLD1 IgGs may have potential applications in serotherapy of H. lepturus envenomation.

Effect of Tityus serrulatus scorpion venom on isolated jejunum: A very useful tool to study the interaction between neurons in the enteric nervous system

Scorpion envenomation is a public health problem in tropical and subtropical areas. In Brazil, Tityus serrulatus is the biggest cause of accidents with venomous animals. Tityus serrulatus venom causes symptoms related to a great activation of the autonomic system attributed to a massive release of sympathetic and parasympathetic mediators. This effect is attributed to the presence of toxins acting in Na+ and K+ ion channels, leading to an increase in cell excitability. Although gastrointestinal symptoms, like diarrhoea and sialorrhea, is observed in moderate to severe cases, little attention is given in clinical reports. Gastrointestinal motility is controlled by the enteric nervous system which is composed of a wide variety of interconnected neurons that are influenced by the sympathetic and parasympathetic nervous systems. Thus, this work aimed to characterize the effects of Tityus serrulatus venom on sympathetic and parasympathetic neurotransmission of rat jejunum, as well as to investigate possibles effects on other neurons of the enteric nervous system. To this, we verify the effects of Tityus serrulatus venom on the contractility of isolated rat jejunum through organ-bath experiments. We observed that venom can induce both contraction and relaxation. The contraction was partially inhibited by atropine (1 μM) and by suramin (0.1mM) through tetrodotoxin-resistant and sensitive mechanisms. The relaxation was completely inhibited by 3 μM propranolol and partially inhibited by 1 μM phentolamine. Suramin induced a slowing of relaxation curve. Tetrodotoxin completely inhibits the relaxation induced by Tityus serrulatus venom, but the contraction curves were only partially reduced in their initial portion. The final part of the curve was largely enhanced by Tetrodotoxin. Atropine blocks almost completely the contraction curve in the presence of Tetrodotoxin. These results indicate that Tityus serrulatus venom induces the release of both excitatory (predominantly acetylcholine) and inhibitory (mainly noradrenaline) neurotransmitters. The effects of Tityus serrulatus venom on organ contractility was quite complex and seem to derive from a diffuse and nonspecific release of mediators from autonomic and enteric nervous systems. Further investigation of venom action and its isolated toxins can reveal important aspects to deepen our knowledge about the enteric nervous system transmission and the interaction between excitatory and inhibitory mediators as well as the physiological role of Na+ and K+ ion channels in gut motility.

Dobutamine in the treatment of severe scorpion envenoming

Scorpion envenoming is a frequent and deadly event in Tunisia. It is caused mainly by Androctonus australis and Buthus occitanus. Pulmonary edema and shock following scorpion envenoming are related to adrenergic cardiomyopathy, and are the main symptoms leading to death. Our aim was to search for the effect of dobutamine on “scorpion myocardiopathy” and to define the optimal dose of dobutamine to start with. This study was conducted in the medical surgical ICU of Habib Bourguiba University Hospital in Sfax - Tunisia. We included 21 patients with pulmonary edema or hemodynamic shock following scorpion envenoming. All patients were monitored using Swan-Ganz catheter. After a first check of the hemodynamic parameters (baseline), all patients received dobutamine infusion at 5, 10, and 15 μg/kg/min. The median age of patients was 19 years (IQR: 14–26) and 12 patients (57.1%) were males. On ICU admission, 11 patients (52.4%) had shock, all patients (100%) had pulmonary edema, 20 patients (95.2%) had neurologic manifestations, and 16 patients (76.2%) had gastro-intestinal manifestations. During ICU stay, 18 patients (85.7%) received mechanical ventilation (MV). The median duration of MV was 3 days (IQR: 2–4). The median duration of dobutamine administration was 4 days (IQR: 3–5). Cardiac index at baseline was 2.7 L/min/m2 (IQR: 2.3–3.2). Under dobutamine at 5, 10 and 15 μg/kg/min, it was 3.6 (IQR: 3.2–3.9), 4.0 (IQR: 2.9–4.8), and 4.1 (IQR: 3.6–4.9) respectively. Arterio-venous oxygen difference at baseline was 6.0 ml/dl (IQR: 5.0–7.0). Under dobutamine at 5, 10 and 15 μg/kg/min, it was 6.1 (IQR: 4.7–6.4), 3.9 (IQR: 3.4–4.3), and 3.9 (IQR: 3.1–4.7) respectively. The length of stay in ICU was 4 days (IQR: 4–5) and 2 patients died during ICU stay (9.5%). Our study confirms that cardiac dysfunction following scorpion envenomation in Tunisia improved well and safely under dobutamine infusion. The optimal dose of dobutamine to start with was between 5 and 10 μg/kg/min.

Scorpion Venom: Detriments and Benefits.

Scorpion venom may cause severe medical complications and untimely death if injected into the human body. Neurotoxins are the main components of scorpion venom that are known to be responsible for the pathological manifestations of envenoming. Besides neurotoxins, a wide range of other bioactive molecules can be found in scorpion venoms. Advances in separation, characterization, and biotechnological approaches have enabled not only the development of more effective treatments against scorpion envenomings, but have also led to the discovery of several scorpion venom peptides with interesting therapeutic properties. Thus, scorpion venom may not only be a medical threat to human health, but could prove to be a valuable source of bioactive molecules that may serve as leads for the development of new therapies against current and emerging diseases. This review presents both the detrimental and beneficial properties of scorpion venom toxins and discusses the newest advances within the development of novel therapies against scorpion envenoming and the therapeutic perspectives for scorpion toxins in drug discovery.

Synthetic peptides to produce antivenoms against the Cys-rich toxins of arachnids.

Scorpion and spider envenomation is treated with the appropriate antivenoms, prepared as described by Césaire Auguste Phisalix and Albert Calmette in 1894. Such treatment requires the acquisition and manipulation of arachnid venoms, both very complicated procedures.Most of the toxins in the venoms of spiders and scorpions are extremely stable cysteine-rich peptide neurotoxins. Many strategies have been developed to obtain synthetic immunogens to facilitate the production of antivenoms against these toxins. For example, whole peptide toxins can be synthesized by solid-phase peptide synthesis (SPPS). Also, epitopes of the toxins can be identified and after the chemical synthesis of these peptide epitopes by SPPS, they can be coupled to protein carriers to develop efficient immunogens. Moreover, multiple antigenic peptides with a polylysine core can be designed and synthesized.This review focuses on the strategies developed to obtain synthetic immunogens for the production of antivenoms against the toxic Cys-rich peptides of scorpions and spiders.

Review of Scorpion Stings and Snakebites Treated by the French Military Health Service During Overseas Operations Between 2015 and 2017

Depending on their theatre of operation, French soldiers may potentially be exposed to scorpion stings and snakebites. Following the recommendations of a French military health service (FMHS) technical committee for envenomation, the FMHS provides antivenoms appropriate to each deployment. This work aimed to evaluate this risk of envenomation and to assess the antivenoms used by the FMHS in operational theatres since the creation of this committee in 2015. Cases were identified based on a review of temporary authorization of use application forms for the use of antivenom. Data were collected retrospectively from these forms, and prescribing physicians were contacted for any missing data. Between 2015 and 2017, 28 requests for temporary authorization of use were identified: 19 for Scorpifav (Sanofi-Pasteur, Lyon, France) and 9 for Fav-Afrique (Sanofi-Pasteur). The FMHS treated 15 soldiers and 4 civilians for scorpion envenomation with Scorpifav: 15 in Mali, 3 in Chad, and 1 in Niger. Systemic signs were observed in 7 patients. Two soldiers and 7 civilians were treated with Fav-Afrique for ophidian envenomation: 5 in Djibouti, 3 in Mali, and 1 in the Republic of Côte d'Ivoire. These 28 patients were treated without sequelae. Other than moderate erythema that resolved with an antihistamine, no adverse effects were reported. Medical evacuation to France was unnecessary. This study shows that the risk of envenomation for soldiers on deployment is low but real. Antivenoms used by the FMHS were efficient and well tolerated, preserving the operational capacity of deployed troops.

Novel Mutant Phospholipase D from Hemiscorpius lepturus Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion Venom.

Hemiscorpius lepturus (H. lepturus) which belongs to the Scorpionidae family, is the deadliest scorpion in Iran. It causes pathological manifestations like dermonecrosis, hemolysis, renal failure, necrotic ulcers, and in some cases, even death. The venom of this scorpion is well-known for its cytotoxic effects in comparison with the other venomous scorpions which show significant neurotoxic effects. Due to the painless nature of the sting of this scorpion, the clinical symptoms occur in victims 24 to 72 h post-sting. In our previous studies during the last decade, we demonstrated that the medical complications are attributable to the presence of phospholipase D (PLD) as a major toxin in the venom. With the purpose of designing and constructing a vaccine against H. lepturus for humans, animal model experiments were performed. To achieve this goal, non-toxic PLD was developed by mutation of two critical catalytic residues—His12 and His48—into alanines and the product was then denominated mut-rPLD1. The in-vivo tests showed that the mice immunized with interval doses of 10 µg of mut-rPLD1, were completely protected against 10× the LD100 of the venom. In conclusion, this mutant may be an effective vaccine candidate against scorpion envenomation by H. lepturus in future clinical studies.

Interleukin-1 Receptor-Induced Nitric Oxide Production in the Pancreas Controls Hyperglycemia Caused by Scorpion Envenomation

Tityus serrulatus causes numerous scorpion envenomation accidents and deaths worldwide. The symptoms vary from local to systemic manifestations, culminating in pulmonary edema and cardiogenic shock. Among these events, transitory hyperglycemia is a severe manifestation that influences pulmonary edema, hemodynamic alterations, and cardiac disturbances. However, the molecular mechanism that leads to increased glucose levels after T. serrulatus envenomation remains unknown. This study aimed to investigate our hypothesis that hyperglycemia due to scorpion envenomation involves inflammatory signaling in the pancreas. The present study showed that T. serrulatus venom induces the production of IL-1α and IL-1β in the pancreas, which signal via IL-1R and provoke nitric oxide (NO) production as well as edema in β-cells in islets. Il1r1−/− mice were protected from transitory hyperglycemia and did not present disturbances in insulin levels in the serum. These results suggest that the pathway driven by IL-1α/IL-1β-IL-1R-NO inhibits insulin release by β-cells, which increases systemic glucose concentration during severe scorpion envenomation. A supportive therapy that inhibits NO production, combined with antiserum, may help to prevent fatal outcomes of scorpion envenomation. Our findings provide novel insights into the design of supportive therapy with NO inhibitors combined with antiscorpion venom serum to overcome fatal outcomes of scorpion envenomation.