Efficacy of Indian polyvalent snake antivenoms against Sri Lankan snake venoms: lethality studies or clinically focussed in vitro studies

In vitro antivenom efficacy studies were compared to rodent lethality studies to test two Indian snake antivenoms (VINS and BHARAT) against four Sri Lankan snakes. In vitro efficacy was tested at venom concentrations consistent with human envenoming. Efficacy was compared statistically for one batch from each manufacturer where multiple vials were available. In binding studies EC₅₀ for all VINS antivenoms were less than BHARAT for D. russelii [553 μg/mL vs. 1371 μg/mL;p=0.016), but were greater for VINS antivenoms compared to BHARAT for N. naja [336 μg/mL vs. 70 μg/mL;p<0.0001]. EC₅₀ of both antivenoms was only slighty different for E. carinatus and B. caeruleus. For procoagulant activity neutralisation, the EC₅₀ was lower for VINS compared to BHARAT - 60 µg/mL vs. 176 µg/mL (p<0.0001) for Russell's viper and 357 µg/mL vs. 6906µg/mL (p<0.0001) for Saw-scaled viper. Only VINS antivenom neutralized in vitro neurotoxicity of krait venom. Both antivenoms partially neutralized cobra and didn't neutralize Russell's viper neurotoxicity. Lethality studies found no statistically significant difference in ED₅₀ values between VINS and BHARAT antivenoms. VINS antivenoms appeared superior to BHARAT at concentrations equivalent to administering 10 vials antivenom, based on binding and neutralisation studies. Lethality studies were inconsistent suggesting rodent death may not measure relevant efficacy outcomes in humans.