Matthew Graham

Scorpions of the Neotropical genus Tityus are responsible for most severe envenomations in the Caribbean, South America, and Lower Central America (LCA). Although Tityus is taxonomically complex, contains high toxin polymorphism, and produces variable clinical manifestations, treatment is limited to antivenoms produced against species with restricted distributions. In this study, we explored the compositional and antigenic diversity of Tityus venoms to provide improved guidelines for the use of available antivenoms at a broader geographic scale. We used immunoblotting, competitive ELISA, and in vivo studies to compare reactivity against commercial antivenoms from Brazil, Venezuela, and Mexico, as well as MALDI-TOF mass spectrometry, cDNA sequencing, and phylogenetic analyses to assess venom sodium channel-active toxin (NaTx) content from medically important Tityus populations inhabiting Brazil, Colombia, Costa Rica, Ecuador, Panama, Trinidad and Tobago, and Venezuela. Additionally, we raised rabbit antibodies against Tityus venoms from LCA to test for cross-reactivity with congeneric species. The results suggest that Tityus spp. possess high venom antigenic diversity, underlying the existence of four toxinological regions in Tropical America, based on venom composition and immunochemical criteria: LCA/Colombia/Amazonia (Region I), Venezuela (Region II), southeast South America (Region III), and a fourth region encompassing species related to toxinologically divergent Tityus cerroazul. Importantly, our molecular and cross-reactivity results highlight the need for new antivenoms against species inhabiting Region I, where scorpions may produce venoms that are not significantly reactive against available antivenoms

Scorpion envenoming by species in the genus Tityus is hereby reported from rural locations in the Amazonian province of Morona Santiago, southeastern Ecuador. Twenty envenoming cases (18 patients under 15 years of age) including one death (a 4-year-old male) were recorded at the Macas General Hospital, Morona Santiago, between January 2015 and December 2016 from the counties of Taisha (n = 17), Huamboyo (n = 1), Palora (n = 1), and Logroño (n = 1). An additional fatality from 2014 (a 3-year-old female from Nayantza, Taisha county) is also reported. Leukocytosis and low serum potassium levels were detected in most patients. We observed a significant negative correlation between leukocytosis and hypokalemia. Scorpions involved in three accidents from Macuma, Taisha County, were identified as genetically related to Tityus obscurus from the Brazilian Amazonian region based on comparison of mitochondrial DNA sequences encoding cytochrome oxi-dase subunit I. These cases, along with previously reported envenoming from northern Manabí, reinforce the notion that scorpionism is a health hazard for children in Ecuador and emphasizes the need to supply effective antivenoms against local species, which are not currently available. The genetic affinity of the Ecuadorian specimens with T. obscurus may underlay toxinological, clinical, and venom antigenic relationships among Amazonian scorpions that deserves further exploration for designing therapeutic strategies to treat scorpionism in the region.

Two new species of Euscorpius Thorell, 1876 (subgenus Euscorpius s.str.) (Scorpiones: Euscorpiidae) are described based on morphology and the COI DNA barcoding marker: E. deltshevi sp. n. from northern Bulgaria and neighbouring Serbia (formerly reported as E. carpathicus) and E. solegladi sp. n. from southwestern Bulgaria and neighbouring Greece (formerly reported as E. hadzii).

This chapter assesses the phylogenetic relationships between scorpions and sodium channel-active scorpion toxins (NaScTx) of medical significance, almost entirely contained within the family Buthidae, with the exception of Hemiscorpius lepturus (Hemiscorpiidae). Within Buthidae, venom capable
of severe and lethal scorpionism appears to have evolved multiple times among and within major morphological groups. Published mitochondrial sequence data from two markers (COI & 16S) were used to construct a partial maximum likelihood phylogeny for Buthidae. The resulting topology is largely congruent with results from comparative analysis of morphological data. Old World and New World buthids appear to be split, suggesting that some of the higher-level
patterns in Buthidae can be explained by the breakup of Pangea. Provided that the venom composition should be more similar among closely related than distant species, the phylogeny can be used to predict which of the less dangerous
species could also produce potent venoms. Clinical, phylogenetic, and toxinological evidence were also used to interpret the evolution and biogeography of these medically significant venomous taxa and the evolution of their toxic
molecules. The existence of species-specific NaScTx repertoires in scorpions is probably the consequence of coevolution and arms races at the molecular and biochemical levels to overcome the ever-evolving structure of receptor sites
(including sodium channels) in their predators and preys.