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

Abstract

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.

Fig 1. Medically relevant Category I snakes in North Africa and the Middle East.

(A) Phylogeny and geographic distribution and (B) reported toxicity and available venom proteome or transcriptome (⁺) data are shown. Specifically, the table presents the genera, species, the origin of the reference proteome or transcriptome, and the median lethal dose in mice (LD₅₀; mg/kg) [–46]. It also illustrates the relative abundance of 3FTxs, PLA₂s, SVMPs, SVSPs, LAAOs, KSPIs, CRiSPs, DISs, NPs, and CTLs. All components are represented as relative wet weight abundance in %. Notably, snake venom composition may vary depending on region. 3FTx, three-finger toxin; CRiSP, cysteine-rich secretory protein; CTL, C-type lectin; DIS, disintegrin; KSPI, kunitz-type serine protease inhibitor; LAAO, L-amino acid oxidase; NP, natriuretic peptide; PLA₂s, phospholipase A₂s; SVMP, snake venom metalloprotease; SVSP, snake venom serine protease.

Fig 2. Medically important scorpions in North Africa and the Middle East.

(A) Phylogeny and geographic distribution and (B) reported toxicity and available venom proteome or transcriptome (⁺) data are shown [–91]. Specifically, the table presents the genera, species, the origin of the reference proteome or transcriptome, and the median lethal dose in mice (LD₅₀; mg/kg). It also illustrates the relative abundance of toxins acting on Na⁺ channels (NaTx), toxins acting on K⁺ channels (KTxs), toxins acting on Ca²⁺ channels (CaTxs), toxins acting on Cl⁻ channels (ClTxs), VSPs, VMPs, PLA₂s, HYALs, PIs, HDPs, La1s, antigen-5 and CAPs, IGFBPs, BPPs, KSPIs, NDBPs (e.g., BmKa2s), and other (often a result of lacking data). All components are represented as relative wet weight abundance in %. Notably, scorpion venom composition may vary depending on region. BPP, bradykinin-potentiating peptide; CAP, pathogenesis-related protein; HDP, host defense peptide; HYAL, hyaluronidase; IGFBP, insulin-like growth factor binding protein; KSPI, kunitz-type serine protease inhibitor; La1, La1 peptide; NDBP, non-disulfide-bridged peptide; PI, protease inhibitor; PLA₂, phospholipase A₂; VMP, venom metalloproteinase; VSP, venom serine protease.

Fig 3. Medically relevant spiders in North Africa and the Middle East.

(A) Phylogeny and geographic distribution and (B) reported toxicity and available venom proteome or transcriptome (⁺) data are shown [–149]. Specifically, the table presents the genera, species, the origin of the reference proteome or transcriptome, and the median lethal dose in mice (LD₅₀; mg/kg). It also illustrates the relative abundance of LTxs, Latrodectins, PLDs, ICKs (Knottins), CRiSPs, VMPs, VSPs, HYALs, and lipases. All components are represented as relative wet weight abundance in %. *proxy from Loxosceles intermedia was used. Notably, spider venom composition may vary depending on region. CRiSP, cysteine-rich secretory protein; HYAL, hyaluronidase; LTx, latrotoxin; PLD, phospholipase-D; VMP, venom metalloproteinase; VSP, venom serine protease.

Fig 4. Country-specific overview of the epidemiology of snakebite (A) and scorpion stings (B) in the MENA region.

The country-specific data were obtained from epidemiological literature covering the past 25 years (1995 to 2020). The data represent absolute numbers, and details can be found in S1 Table. MENA, Middle East and North Africa.