Induced pathophysiological alterations by the venoms of the most dangerous Moroccan scorpions Androctonus mauretanicus and Buthus occitanus: A comparative pathophysiological and toxic-symptoms study.

Scorpion envenomation is a serious public health issue. Androctonus mauretanicus (Am) and Buthus occitanus (Bo) are the most dangerous scorpions in Morocco. Despite their medical relevance, no study has yet related their kinetics of symptom apparition and the consequent tissue disorders at the same interval post-injection. This work achieved the first comparative pathophysiological and toxic-symptoms study between the Am and Bo venoms from a biochemical, toxicological and physiopathological standpoint. The activity of venoms and their subletal dose were determined by administration of increasing concentrations of the venoms. 30, 60 and 120 min following the experimental envenomation in mice, the profile of clinical symptoms was underlined and the main organs: brain, heart, lungs, liver and kidneys were removed for histological examination. The Am venom is a rich source of proteins and three-times more toxic than the Bo. The most observed clinical symptoms are neurological and cardiopulmonary. The Am venom caused histopathological alterations at 30, 60, and 120 min which were more important than the Bo. This study highlighted that both venoms exhibited a strong toxicity with variable intensities. Moreover, we showed the presence of correlation between the level of histopathological disorders observed and the intensity of signs appeared at the same time following venom inoculation.

Terrestrial venomous animals, the envenomings they cause, and treatment perspectives in the Middle East and North Africa.

The Middle East and Northern Africa, collectively known as the MENA region, are inhabited by a plethora of venomous animals that cause up to 420,000 bites and stings each year. To understand the resultant health burden and the key variables affecting it, this review describes the epidemiology of snake, scorpion, and spider envenomings primarily based on heterogenous hospital data in the MENA region and the pathologies associated with their venoms. In addition, we discuss the venom composition and the key medically relevant toxins of these venomous animals, and, finally, the antivenoms that are currently in use to counteract them. Unlike Asia and sub-Saharan Africa, scorpion stings are significantly more common (approximately 350,000 cases/year) than snakebites (approximately 70,000 cases/year) and present the most significant contributor to the overall health burden of envenomings, with spider bites being negligible. However, this review also indicates that there is a substantial lack of high-quality envenoming data available for the MENA region, rendering many of these estimates speculative. Our understanding of the venoms and the toxins they contain is also incomplete, but already presents clear trends. For instance, the majority of snake venoms contain snake venom metalloproteinases, while sodium channel-binding toxins and potassium channel-binding toxins are the scorpion toxins that cause most health-related challenges. There also currently exist a plethora of antivenoms, yet only few are clinically validated, and their high cost and limited availability present a substantial health challenge. Yet, some of the insights presented in this review might help direct future research and policy efforts toward the appropriate prioritization of efforts and aid the development of future therapeutic solutions, such as next-generation antivenoms.

Comparison of the Scorpionism Caused by Centruroidesmargaritatus, Tityuspachyurus and Tityus n. sp. aff. metuendus Scorpion Venoms in Colombia.

Among other scorpion species, Colombia has two genera of the Buthidae family Centruroides and Tityus, considered to be dangerous to humans. This research shares scientific knowledge aiming to a better understanding about the pathophysiological effects of such venoms. The venom of the three species: Centruroides margaritarus, Tityus pachyurus, and T. n. sp. aff. metuendus with biomedical interest were studied. An initial pre-glycemic sample was taken from ICR mice. They were later intraperitoneally inoculated with doses of 35% and 70% of LD50 of total venom. Poisoning signs were observed during a 6-h period to determine the level of scorpionism. After observation, a second glycemic sample was taken, and a histopathological evaluation of different organs was performed. This work revealed that all three venoms showed considerably notorious histopathological alterations in main organs such as heart and lungs; and inducing multiple organ failure, in relation to the glycemia values, only C. margaritatus and T. n. sp. aff. metuendus showed significant changes through manifestation of hyperglycemia. According to the Colombian scorpionism level; signs were mild to severe affecting the autonomous nervous system.

Hand ulceration.

In the American Southwest, a common problem can be diagnosed with the knowledge of the local environment and its inhabitants.

Scorpion sting: N-terminal fragment of proB-type natriuretic peptide as an early predictor of pediatric cardiotoxicity.

AIM OF THE WORK: This prospective study was conducted to evaluate the clinical reliability of N-terminal fragment of proB-type natriuretic peptide (NT-proBNP) in identifying patients with cardiotoxicity in the early hours following scorpion sting. SUBJECTS AND METHODS: This study involved 483 children aging between 2-17 years who were admitted to Minia University Poisoning Control Center from 1st January 2010 to 31st December 2019 with a history of scorpion sting, and on clinical evaluation symptoms were manifested. All subjects were clinically examined, investigated for NT-proBNP and CPK-MB on admission, 6 h and 24 h post-envenomation; and subjected to 24 h cardiac monitoring with periodic ECG every 6 h. RESULTS: Assessment of CPK-MB levels showed a significant increase in all moderate to severe cases 6 h post-envenomation. Assessment of NT-proBNP levels showed a significant increase in all moderate to severe cases on admission and 6 h post-envenomation. Moreover, there was a significant decrease in the NT-proBNP level after 24 h compared with that measured on admission. The sensitivity of NT-proBNP for the diagnosis of myocardial injury at hospital admission was significantly higher than that of CPK-MB. CONCLUSION: NT-proBNP may be a valuable and sensitive laboratory biomarker to predict cardiotoxicity of scorpion sting in the early hours.

What's eating you? the South African fattail scorpion revisited.

Worldwide, there are more than 3250 deaths a year related to scorpion stings. With the increasing popularity of exotic and dangerous pets, American physicians are more likely to see exotic scorpion envenomations. Although adults are stung more often, children experience more severe envenomation.

Venoms of Iranian Scorpions (Arachnida, Scorpiones) and Their Potential for Drug Discovery.

Scorpions, a characteristic group of arthropods, are among the earliest diverging arachnids, dating back almost 440 million years. One of the many interesting aspects of scorpions is that they have venom arsenals for capturing prey and defending against predators, which may play a critical role in their evolutionary success. Unfortunately, however, scorpion envenomation represents a serious health problem in several countries, including Iran. Iran is acknowledged as an area with a high richness of scorpion species and families. The diversity of the scorpion fauna in Iran is the subject of this review, in which we report a total of 78 species and subspecies in 19 genera and four families. We also list some of the toxins or genes studied from five species, including Androctonus crassicauda, Hottentotta zagrosensis, Mesobuthus phillipsi, Odontobuthus doriae, and Hemiscorpius lepturus, in the Buthidae and Hemiscorpiidae families. Lastly, we review the diverse functions of typical toxins from the Iranian scorpion species, including their medical applications.

Approach to scorpion stings in pregnancy: A retrospective case series and literature review.

OBJECTIVE: Scorpion stings remain a serious health problem in many parts of the world. There is very limited information regarding the effects of therapies delivered for scorpion stings in pregnant women on the mother and fetus. They can cause acute conditions such as fetal loss, preterm delivery, or placental abnormalities and can also result in other conditions that may have an effect on the baby in the long term. MATERIALS AND METHODS: In this study the medical records of 24 pregnant women who were admitted to the emergency room at Suruç State Hospital due to scorpion stings between January 1, 2013 and January 1, 2014 were retrospectively reviewed. Age, gestational week, monthly distribution of the cases, type of delivery, status of the fetus, affected body sites, and local and systemic findings were evaluated. The clinical severity of each case was assessed using Abroug's classification. A fetal biophysical profile test was administered in pregnant women above 24 weeks of gestation. The newborns underwent follow-up for mental and motor functions in the pediatric department at three-month intervals for 12 months. RESULTS: 24 patients, with a mean age of 26.1 ± 2.4 years, were included in the study. The most common region stung by scorpions was Lower extremity (58.3%). The most common symptom occurred in cases was immediate localized pain (58%). In terms of gestational age, 41.6% of scorpion sting were within the third trimester. Biophysical profile scores were 8 and above. Only symptomatic treatment, without use of anti-venom, was done to all the patients in this study. And neither death nor major sequel happened. CONCLUSION: Scorpion stings during pregnancy may not have significant adverse effects on the fetus and the mother. Decisions regarding the use of anti-venom in pregnant women should be considered carefully when only limited safety information, especially in those patients with only local symptoms.

Myocarditis and Early Markers of Cardiac Response Associated with Scorpion Stings in Children.

INTRODUCTION: A clinical course ranging from mild local findings to life-threatening systemic findings may occur after scorpion stings. The purpose of this study was to identify priority markers indicating scorpion sting-related cardiac involvement. METHODS: Our study was performed between July 2014, and September 2015 in the Çukurova University medical faculty pediatric emergency department, in Adana, Turkey. Patients admitted with scorpion sting-related cardiac involvement and a control group consisting of patients with no scorpion sting-related cardiac involvement were included in the study. Troponin I at time of presentation and at 6 and 24 h, N-terminal prohormone of brain natriuretic peptide (NTproBNP), ejection fraction as determined by echocardiography at 24 h, and peak and end of T wave (Tp-e) and Tp-e/QTc ratios with echocardiography at 24 h were evaluated. RESULTS: A patient group consisting of 7 cases of scorpion envenomation-related myocarditis and a control group of 30 cases of scorpion intoxication without myocarditis findings were enrolled. Statistically significantly high glucose, white blood cell values, creatine kinase MB, troponin I, and NTproBNP values were identified in the scorpion sting-related myocarditis group (P<0.05). Ejection fractions determined by echocardiography at time of presentation were significantly lower in the patients with myocarditis compared with the control group (P<0.05). A statistically significant difference was identified between Tp-e/corrected QT interval (QTc) ratios investigated in DI and V2 derivations in patient and control group echocardiograms (P<0.05). CONCLUSIONS: We think that use can be made of NTproBNP in addition to echocardiography and troponin I in the early diagnosis of scorpion sting-related myocarditis and that Tp-e and Tp-e/QTc ratios identified via echocardiography can be used as early markers; however, further studies with larger numbers are needed to confirm this.

North American scorpion species of public health importance with a reappraisal of historical epidemiology.

Scorpionism is a severe threat to public health in North America. Historically, few species of Centruroides have been considered to be the offending taxa, but we know now that their diversity is greater and our knowledge incomplete. Current distribution maps are inadequate for some species. Epidemiologic studies are sporadic and local, and a complete synthesis for North America is missing. We analyze historical and recent knowledge about the identity, distribution and epidemiology of species of medical importance in North America. PubMed, Google Scholar, the National Collection of Arachnids, and results of recent field work were consulted in the preparation of our analysis. We recognized 21 species and one subspecies of medically important scorpions in need of precise geographical delimitation. All these species are found in Mexico, which is clearly a hotspot for scorpionism. Although mortality has been steadily decreasing, deaths still occur, and morbidity remains high. Mortality is most common at age classes of 0-10 years and >50. Morbidity is highest in age class 15-50 years, including the most economically active segment of the population. The season of the highest incidence of scorpion sting peaks between spring and summer but there appears to be a second, lower peak at the end of the summer. Although the systematics of the genus Centruroides has advanced considerably, our knowledge of its diversity remains fragmentary. There is a disconnection between the actual distribution of the scorpions and the incidence maps constructed from scorpion sting records. Despite a historically robust knowledge of the distribution of well-known species, most recently described species are known from only a few localities. Some of the epidemiological parameters are consistent among studies reported herein.

Scorpion bite-induced unilateral pulmonary oedema.

A 24-year-old woman came to the emergency room of our hospital, 6 hours after a sting to the pulp of her middle finger of her left upper limb by an Indian red scorpion. On examination, she had tachycardia, tachypnoea, hypotension and low oxygen saturation at room temperature. On auscultation, there was poor air entry in all areas of the right lung along with crackles. The left lung field was normal on auscultation. Chest X-ray showed unilateral haziness of right lung field. Two-dimensional echocardiography showed clinical findings of myocarditis. Arterial blood gas showed metabolic acidosis with severe hypoxaemia, suggestive of type 1 respiratory failure. After intubation and initiating ventillatory support, the patient was given intravenous analgesics, antihistaminic and infiltrated of site of bite with 2% xylocaine. The patient was started on inotropes, alpha receptor blocker, intravenous steroids, bronchodilators and diuretics support. The patient clinically improved over the course of treatment and was subsequently discharged.

Second Dose of Scorpion Antivenom in Children with Indian Red Scorpion (Mesobuthus tamulus) Sting Envenomation.

OBJECTIVE: To study the effect of the second dose of scorpion antivenom in children with non-resolving or worsening scorpion sting envenomation. METHODS: 72 children aged ≤12 years with scorpion sting envenomation grade 2 and above were enrolled. 61 received the first dose of three vials of antivenom at admission (group A). Children with persistent/worsening envenomation at 6 hours received the second dose (group B). The time required for resolution of autonomic symptoms, myocardial dysfunction, predictors of the second dose and side effects were studied. RESULTS: The mean time taken for resolution of autonomic symptoms were similar in GroupA and B (4.1 vs. 5.3 hours, P=0.452), and of myocardial dysfunction was shorter in Group A (10.8 vs. 37.6 hours, P=0.019). On regression analysis, abnormal echocardiography at admission was found to be a significant predictor of the second dose (OR=27.6, 95% CI, 4.7-162.5; P=<0.001). CONCLUSION: Children with severe scorpion sting envenomation with abnormal echocardiography may require a higher dose of scorpion antivenom.

Severe bark scorpion envenomation in adults.

INTRODUCTION: The preponderance of medical literature regarding severe bark scorpion envenomation describes pediatric patients; however, the majority (>66%) of annual poison center calls pertain to adults. This retrospective review sought to evaluate the clinical manifestations of adults with severe Centruroides sculpturatus envenomation and determine if significant morbidity occurred. METHODS: This is a retrospective review of adults presenting to a single tertiary referral center with Grade-III or Grade-IV scorpion envenomation from 1 January 2007 to 3 March 2013. The primary objective is to describe clinical findings, treatment strategies, complications and short-term outcomes. RESULTS: Thirty-three patients were included; 61% were female (20/33), average age was 40.7 (19-81) years. The average time to healthcare facility was 142 (14-720) minutes. The most common signs and symptoms of envenomation were: pain/paresthesias 94%, opsoclonus 82%, excessive motor activity 76%, visual disturbance 76%. Benzodiazepines 85% (29/33) and opioids 83% (28/33) were the most frequently used agents to control envenomation. Cardiac evaluation was performed in 24% of patients, 6% were pregnant and underwent fetal monitoring, 6% were intubated and 3% developed rhabdomyolysis. Average length of stay (LOS) was 28.3 (1.5-307) hours; 58% (19/33) required hospital admission. Four patients had LOS >48 h, with pre-existing cardiac disease, substance misuse disorder, acute ethanol withdrawal and medical errors identified as factors contributing to prolonged LOS. CONCLUSIONS: Bark scorpion envenomation in adults may be severe, necessitating medical intervention and hospital admission. Comorbid conditions and complications arising from treatment may contribute to prolonged LOS.

Severe scorpion envenomation: pathophysiology and the role of inflammation in multiple organ failure.

Scorpion stings occur on every continent except Antarctica. The correlation between young age and severity of clinical manifestations after this envenomation is well-established. Several studies have emphasized the relevance of pro-inflammatory mediators in the pathophysiological manifestations of human scorpion envenomation. Moreover, there is a significant association between pro-inflammatory cytokine levels in the blood and the severity of scorpion envenomation. Release of these cytokines increases the severity of the visceral damage induced by the direct action of the venom and the activation of both the sympathetic and parasympathetic nervous systems.

Functional up-regulation of Nav1.8 sodium channel on dorsal root ganglia neurons contributes to the induction of scorpion sting pain.

BmK I, purified from the venom of scorpion Buthus martensi Karsch (BmK), is a receptor site-3-specific modulator of voltage-gated sodium channels (VGSCs) and can induce pain-related behaviors in rats. The tetrodotoxin-resistant (TTX-R) sodium channel Nav1.8 contributes to most of the sodium current underlying the action potential upstroke in dorsal root ganglia (DRG) neurons and may serve as a critical ion channel targeted by BmK I. Herein, using electrophysiological, molecular, and behavioral approaches, we investigated whether the aberrant expression of Nav1.8 in DRG contributes to generation of pain induced by BmK I. The expression of Nav1.8 was found to be significantly increased at both mRNA and protein levels following intraplantar injection of BmK I in rats. In addition, the current density of TTX-R Nav1.8 sodium channel is significantly increased and the gating kinetics of Nav1.8 is also altered in DRG neurons from BmK I-treated rats. Furthermore, spontaneous pain and mechanical allodynia, but not thermal hyperalgesia induced by BmK I, are significantly alleviated through either blockade of the Nav1.8 sodium channel by its selective blocker A-803467 or knockdown of the Nav1.8 expression in DRG by antisense oligodeoxynucleotide (AS-ODN) targeting Nav1.8 in rats. Finally, BmK I was shown to induce enhanced pain behaviors in complete freund's adjuvant (CFA)-inflamed rats, which was partly due to the over-expression of Nav1.8 in DRG. Our results suggest that functional up-regulation of Nav1.8 channel on DRG neurons contributes to the development of BmK I-induced pain in rats.

Scorpionism in Ecuador: First report of severe and fatal envenoming cases from northern Manabí by Tityus asthenes Pocock.

The presence in rural areas of western Ecuador of scorpions in the genus Tityus capable of producing pediatric mortality is hereby evidenced. The medical significance of scorpions in Ecuador has been underestimated partly because of the clinically unimportant stings delivered by Centruroides margaritatus and Teuthraustes atramentarius, which have venom with low toxicity to vertebrates. Five intra-domiciliary cases of scorpion envenoming in victims aged between 1.9 and 16 years old, including one fatality, are reported from rural settings in forest areas of Chone (n = 2) and Flavio Alfaro (n = 3) counties, northern Manabí province, western Ecuador. Three cases were graded as Class II (moderate) and two in Class III (severe) envenoming. Manifestations showed characteristic autonomic nervous system hyper-stimulation and the fatality (a 1.9-year-old boy from Flavio Alfaro) was due to cardio-respiratory failure. Marked leukocytosis in four of the cases (21,800-31,800 cells/mm(3)), with notable neutrophilia (58-82%), suggests induction of a venom-mediated systemic inflammatory response-like syndrome. Specimens responsible for cases in Flavio Alfaro County, including the fatality, were classified as Tityus asthenes Pocock, accountable for severe scorpionism in Colombia. These findings demand implementation of control and therapeutic measures in affected areas in Ecuador, including evaluation of available scorpion antivenoms.

Scorpion-related cardiomyopathy: Clinical characteristics, pathophysiology, and treatment.

CONTEXT: Scorpion envenomation is a threat to more than 2 billion people worldwide with an annual sting number exceeding one million. Acute heart failure presenting as cardiogenic shock or pulmonary edema, or both is the most severe presentation of scorpion envenomation accounting for 0.27% lethality rate. OBJECTIVE: The purpose of this review is to characterize the scorpion-related cardiomyopathy, clarify its pathophysiological mechanisms, and describe potentially useful treatments in this particular context. METHODS: We searched major databases on observational or interventional studies (whether clinical or experimental) on the cardiorespiratory consequences of scorpion envenomation and their treatment. No limit of age or language was imposed. A critical appraisal of the literature was conducted in order to provide a pathophysiological scheme that reconciles reported patterns of cardiovascular toxicity and hypotheses and assumptions made so far. RESULTS: Early cardiovascular dysfunction is related to the so-called "vascular phase" of scorpion envenomation, which is related to a profound catecholamine-related vasoconstriction leading to a sharp increase in left ventricular (LV) afterload, thereby impeding LV emptying, and increasing LV filling pressure. Following this vascular phase, a myocardial phase occurs, characterized by a striking alteration in LV contractility (myocardial stunning), low cardiac output, and hypotensive state. The right ventricle involvement is symmetric to that of LV with a profound and reversible alteration in right ventricular performance. This phase is unique in that it is reversible spontaneously or under inotropic treatment. Scorpion myocardiopathy combines the features of takotsubo myocardiopathy (or stress myocardiopathy) which is linked to a massive release in catecholamines leading to myocardial ischemia through coronary vasomotor abnormalities (epicardial coronary spasm and/or increase in coronary microvascular resistance). Treatment of pulmonary edema due to scorpion envenomation follows the same principles as those applied for the treatment of cardiogenic pulmonary edema in general: this begins with oxygen supplementation targeting an oxygen saturation of 92% or more, by oxygen mask, continuous positive airway pressure, noninvasive ventilation, or conventional mechanical ventilation. Dobutamine effectively improves hemodynamic parameters and may reduce mortality in severe scorpion envenomation. CONCLUSION: Scorpion cardiomyopathy is characterized by a marked and reversible alteration in biventricular performance. Supportive treatment relying on ventilatory support and dobutamine infusion is a bridge toward recovery in the majority of patients.

Comparison of the neurotoxic and myotoxic effects of two Moroccan scorpion venoms and their neutralization by experimental polyclonal antivenom.

AIMS: Scorpion venoms contain complex mixtures of molecules, including peptides. These peptides specifically bind to various targets, in particular ion channels. Toxins modulating Na(+), K(+), Ca(2+) and Cl(-) currents were described from venoms. The Androctonus and Buthus geni of scorpions are widely distributed in Morocco. Their stings can cause pain, inflammation, necrosis, muscle paralysis and death. The myotoxicity is predominantly associated with neurotoxic effects and is a cause of mortality and morbidity. In this study, pharmacological effects of venoms were investigated in vitro on neuromuscular transmission. MAIN METHODS: Effects of Androctonus mauretanicus (Am) and Buthus occitanus (Bo) venoms were investigated using the chick biventer cervicis nerve-muscle preparations. The protective activity of antivenom was also investigated. The antivenom was made from serum of horse that was hyperimmunized with Bo and Androctonus australis hector (Aah) venoms and one venom from Middle East species (Lq). The protective activity of the antivenom was assessed on the neuromuscular system by using stimulated chick nerve-muscle. The results were compared with lethal activity neutralization in mice. KEY FINDINGS: Am and Bo venoms contain myotoxins and postsynaptic neurotoxins. In agreement with lethal potencies of these venoms in mice, Am venom displays greater neurotoxicity and myotoxicity. The antivenom prevented lethality caused by Am, Bo and Aah venoms. The antivenom did not prevent toxic effects caused by Am venom whereas it neutralized Bo venom. SIGNIFICANCE: Am and Bo venoms contain distinct toxins that are responsible for myotoxicity and neurotoxicity. It would be appropriate to add Am venom to produce more efficient antivenom.