Scorpions are venomous arthropods belonging to the class Arachnida and the order Scorpiones (1). To date, ~2,772 species of scorpions have been described globally, of which around 104 species (3.8%) are considered of medical significance due to their venom toxicity and potential for severe envenomation (2). The majority of medically relevant species belong to the family Buthidae, which includes genera such as Androctonus, Buthus, Buthotus, Leiurus, Mesobuthus, and Parabuthus, found in regions such as Asia, India, the Middle East, and North Africa. Additionally, species from the Tityus genus are prevalent in South America and the Caribbean, while Centruroides species are commonly encountered in Mexico, Central America, and the southwestern United States (3).

Scorpion envenomation, or scorpionism, is recognized as a pressing yet often neglected public health concern, particularly in tropical and subtropical regions. It disproportionately affects rural and socioeconomically disadvantaged communities, where access to timely and adequate medical care is limited (4, 5). The presence of scorpions in human dwellings and workplaces leads to frequent encounters, thereby elevating the risk of envenomation and associated morbidity and mortality (6–8).

Global estimates suggest that over 1.2 million scorpion stings occur annually, resulting in more than 3,000 deaths, with a disproportionately high burden observed in children due to their lower body mass and increased vulnerability to systemic complications (9–11). Mortality is most prevalent in low-resource settings, where delayed access to antivenom and critical care services remains a major barrier. High-incidence countries include Mexico, Brazil, Iran, Algeria, and Morocco, where scorpionism remains endemic and requires targeted preventive and therapeutic strategies (12–15). Table 1 summarizes the number of reported cases, deaths, and incidence rates per 100,000 inhabitants in selected endemic countries and regions.

Scorpion venom is a mixture of lipids, peptides, enzymes, free amino acids, nucleotides, amines, inorganic salts, mucoproteins, heterocyclic components, and various other substances. The composition of the venom can be divided into toxic and non-toxic fractions (3).

The non-toxic fraction includes enzymes such as hyaluronidases, mucopolysaccharides, histamine, and serotonin (3). These components contribute to the overall toxicity of the venom. For instance, hyaluronidase facilitates the spread of toxins by degrading the extracellular matrix and connective tissues surrounding blood vessels at the site of envenomation (3). Histamine plays a role in mediating the inflammatory response (26).

The toxic fraction is mainly composed of neurotoxins, which are capable of depolarizing the membranes of nerve cells through various mechanisms. For example, β-toxins alter the activation of Na⁺ channels by reducing the peak amplitude of sodium currents and shifting the voltage dependence of channel activation toward more hyperpolarized potentials (27). In contrast, α-toxins inhibit sodium channel deactivation, while κ-neurotoxins block potassium channels (28–30). Meanwhile, calciums act as agonists of ryanodine receptors, increasing intracellular calcium levels (30). Phospholipases disrupt cell membranes by hydrolyzing phospholipids, leading to tissue necrosis and hemorrhage (28, 31). Proteases also play a pivotal role in activating venom toxin precursors through post-translational modifications (3). Proteases are involved in the spread of the toxin through the breakdown of matrix molecules. In addition, proteolytic activity has been observed. Some proteases have been shown to disrupt the transport of pancreatic vesicles to the exterior of the organ, causing pancreatitis (32–34).

Toxins targeting ion channels particularly voltage-gated sodium and potassium channels—are the primary mediators of neurotoxicity and are especially abundant in species such as Mesobuthus tamulus, Hottentotta saulcyi, and Tityus serrulatus (28, 35, 36). These toxins can account for up to 76.7% of venom mass in some species (35). Moreover, scorpion venom includes a wide variety of pharmacologically relevant peptides and proteins, such as antimicrobial, antiviral, antifungal, and antimalarial peptides (37).

Other notable components of scorpion venom include bradykinin-potentiating peptides and cysteine-rich secretory proteins, which contribute to prey immobilization and immune modulation (31, 38). Non-peptidic molecules like adenosine and citric acid are also present and may act synergistically to enhance the envenomation process (39). Lipid components, including phospholipids and ceramides, are involved in cellular disruption and may modulate inflammation (36).

The inflammatory response triggered by scorpion venom involves a cascade of cellular events and mediator release. Upon envenomation, innate immune cells recognize venom components via pattern recognition receptors, leading to the activation of pro-inflammatory signaling pathways (7, 40). This interaction initiates intracellular signaling cascades that result in the release of inflammatory mediators (40).

The cytokine profile induced by scorpion envenomation varies by species. For example, Androctonus australis hector induces the production of IL-1β, IL-4, IL-6, IL-10, and TNF-α; Tityus serrulatus induces IL-1β, IL-6, IL-8, IL-10, NO, TNF-α, IL-1α, IL-1β, IFN-γ, and GM-CSF; Centruroides noxius induces IL-1β, IL-1α, IFN-γ, IL-6, IL-10, and TNF-α. In the case of Leiurus quinquestriatus, the cytokines produced include IL-6, IL-8, NO, and TNF-α (7). These cytokines may be implicated in the pathophysiology of envenomation, such as inflammatory manifestations at the site of inoculation and systemic repercussions, such as pulmonary edema and cardiogenic shock (41, 42).

Despite advances in antivenom therapy, the poor immunogenicity of low molecular mass toxins (3–15 kDa) remains a challenge, as these are often not effectively neutralized by commercial antivenoms (35, 43). Proteomic and transcriptomic studies have revealed a vast diversity in venom composition, which is influenced by species, geographic location, sex, age, and environmental conditions (44). On average, a single scorpion species can produce around 150 different venom components, with ~750 scorpion venom proteins currently cataloged in the UniProt Animal Annotation Program. Toxins are classified based on their ion channel targets: sodium (α-NaScTxs, β-NaScTxs), potassium (α-KTx, β-KTx, γ-KTx, κ-KTx), and calcium (calcines) (27).

Elemental analyses of venom from Androctonus bicolor, Androctonus crassicauda, and Leiurus quinquestriatus have identified the presence of numerous elements, including sodium, potassium, calcium, copper, germanium, cerium, scandium, lanthanum, silver, gallium, palladium, zirconium, neodymium, bismuth, beryllium, tellurium, thallium, samarium, dysprosium, gadolinium, erbium, cesium, holmium, ytterbium, praseodymium, rhenium, europium, arsenic, manganese, chromium, iron, iodine, selenium, lithium, yttrium, nickel, lead, rubidium, rhodium, uranium, antimony, ruthenium, magnesium, phosphorus, silicon, bromine, aluminum, zinc, strontium, vanadium, barium, and titanium (45). This compositional complexity highlights the need for continued research to improve therapeutic approaches and explore the pharmacological potential of scorpion venom components.

While it is true that one of the main risk factors for scorpion stings is residence in rural areas, where specific environmental and occupational exposures increase the likelihood of encounters. Activities such as storing and handling firewood are particularly hazardous, as they involve prolonged contact with the ground and outdoor environments where scorpions may reside (8). Similarly, the accumulation of leaves, tools, or construction materials near homes provides ideal microhabitats for scorpions, thereby increasing the risk of stings (8).

Notably, some scorpion species exhibit opportunistic behavior, enabling them to adapt to and colonize disturbed or modified environments. These species can establish high-density populations, reproduce rapidly, and survive extended periods without food, allowing them to thrive even under artificial conditions, such as urban settings (14). A prominent example is Tityus serrulatus, whose geographic distribution has expanded significantly across Brazil, with notable proliferation in urban areas (46).

Santana and Oliveira reported that the majority of scorpion envenomation cases occurred in urban and peri-urban areas (65.5%) (47). Another large-scale study in Brazil analyzing 20,555 cases of scorpion stings found that most incidents took place in urban settings (n = 18,571; 90.35%) (48). Similarly, Furtado et al. (49) observed a high frequency of urban cases (n = 9,625; 86.45%) in the state of Ceará, Brazil.

Another relevant risk factor is the presence of birds in the household environment. The straw used in nests serves as a suitable shelter for scorpions, facilitating their proximity to humans (8, 50). Housing conditions also play a critical role. Dwellings constructed with non-durable materials such as tin, wood, or cardboard roofs and dirt floors are more permeable to scorpion intrusion. Additionally, inadequate structural integrity and proximity to natural scorpion habitats further increase the risk of indoor colonization (5, 50). In rural contexts, children frequently assist in agricultural tasks, which further elevate their exposure and risk of stings (50).

Beyond structural and behavioral determinants, several demographic and environmental factors contribute to the epidemiology of scorpionism. Age is a critical determinant of severity, with children particularly those under 15 years being more susceptible to severe envenomation and fatal outcomes (51–53). Occupational exposure remains a significant risk factor, notably among farmers, homemakers, and individuals who handle firewood or rear domestic animals such as ducks and hens (8, 50).

Temporal patterns also modulate risk: stings are more frequent during warmer seasons and nocturnal hours, coinciding with increased scorpion activity (52). Delays in seeking medical care particularly those exceeding 3 h and the inadequate use of antivenom are associated with increased mortality, especially among pediatric populations (51). Emerging evidence has further suggested a possible link between scorpion envenomation and long-term cardiovascular complications, including the development of dilated cardiomyopathy (54).

Inappropriate use of antivenoms remains a critical concern. Fatal outcomes have been associated with improper antivenom administration (51). A study conducted in Brazil involving 293 envenomation cases found that antivenom was inappropriately prescribed in the majority of treated patients (59.7%). Among these cases, the most frequent error was the administration of a higher number of vials than recommended (124 cases; 72.1%), resulting in a total of 323 vials administered beyond protocol guidelines (47). This misuse may stem from the absence of up-to-date reference materials, ineffective dissemination of treatment protocols, and a lack of regular training in the diagnosis and management of scorpion envenomation (47). However, with proper use of antivenom and timely administration, clinical conditions usually improve rapidly, and plasma venom levels generally become undetectable within an hour of starting treatment. Additionally, antivenom reduces the mortality rate even in cases of severe envenomation. It has also been observed that in critically ill children with neurotoxic effects from scorpion envenomation, intravenous administration of scorpion-specific antivenom resolved the clinical syndrome within 4 h (30, 55, 56).

Scorpionism remains a neglected yet impactful public health issue, disproportionately affecting vulnerable populations in tropical and subtropical regions. Despite its significant global burden, it continues to be overlooked by health authorities and excluded from major international health agendas. Given its epidemiological, social, and economic consequences, scorpionism warrants formal recognition as a neglected tropical disease.

The multifactorial nature of scorpion envenomation shaped by ecological conditions, population vulnerability, health system limitations, and socioeconomic inequalities—demands a coordinated, multisectoral response that integrates environmental management, health education, clinical preparedness, and local antivenom production.

National authorities particularly the ministries of health, education, agriculture, and environment must coordinate efforts to address structural risk factors such as unsafe housing, occupational exposure, and limited access to timely care in rural areas. This includes strengthening regional capacity for antivenom production, improving clinical training in envenomation management, and embedding prevention strategies into school curricula and community programs to foster long-term risk reduction and a culture of awareness and resilience.