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.