Treating doctors had observed an increased number of hospital deaths and reactions to the antivenom. Concerns were raised about the effectiveness of Indian polyvalent antivenoms in Sri Lanka in 2012 and there were sufficient concerns about the efficacy of antivenom for the treatment of Russell’s viper ( Daboia russelii) envenoming that the Government requested independent testing of the antivenoms. However, it will be important to ensure that antivenoms are tested in functional studies of clinically relevant venom effects.Ĭurrently all antivenom used in Sri Lanka is supplied from India and there are limited data regarding the efficacy of Indian antivenoms against Sri Lankan snakes 19. The fields of venomics and antivenomics are also beginning to improve our understanding of the different composition of venoms and their interaction with antivenoms 17, 18. For snakes that cause coagulopathy in humans it would seem more appropriate to test the efficacy of antivenom to neutralise procoagulant venom activity in human plasma, rather than the efficacy of antivenom in preventing death in a rodent. Other in vitro and in vivo investigations are available to test the efficacy of antivenom to neutralise relevant pathophysiological effects induced by snake venoms and may provide more clinically useful information 13, 14, 15, 16. This means that the use of death of a rodent as a test of efficacy for snake venoms that cause coagulopathy is problematic. For example, a recent study has demonstrated that rodent plasma is highly resistant to procoagulant toxins that are highly relevant for human envenoming 12. In contrast, pre-synaptic neurotoxins are important in human envenoming 11, as well as toxins that cause coagulopathy, myotoxicity and nephrotoxicity. However, there are significant animal ethical considerations because of the numbers of animals that are required for these tests and there are concerns about extrapolating the death of a rodent to clinical effects in humans.Īlthough the exact mechanism of venom-induced death is unclear in rodents, death may be due to the effects of post-synaptic neurotoxins or early cardiovascular collapse 10. The World Health Organisation (WHO) recommends the use of median lethal dose (LD 50) and median effective dose (ED 50) for assessing the efficacy of antivenoms 9. In some cases this has led to changes in dosing based on such concerns and in others the development of new antivenoms 8.Ī particular problem with developing antivenoms is testing their efficacy and more importantly the potential efficacy in humans, including appropriate dosing. Over the last two decades there have been concerns about the efficacy of some antivenoms and whether sufficient doses are being used 6, 7. Although antivenom is the accepted treatment for snake envenoming, there is a shortage of antivenoms in Africa and Asia and in some cases this has led to the use of antivenom made in one country being used in a different country, that may not be effective against snake venoms in that geographical region 2, 3, 4, 5.

Snake envenoming is recognised as a major global health issue with large numbers of deaths and cases of envenoming occurring each year in tropical and sub-tropical regions of the world 1. Lethality studies were inconsistent suggesting rodent death may not measure relevant efficacy outcomes in humans. VINS antivenoms appeared superior to BHARAT at concentrations equivalent to administering 10 vials antivenom, based on binding and neutralisation studies. Lethality studies found no statistically significant difference in ED 50 values between VINS and BHARAT antivenoms. Both antivenoms partially neutralized cobra and didn’t neutralize Russell’s viper neurotoxicity. Only VINS antivenom neutralized in vitro neurotoxicity of krait venom. For procoagulant activity neutralisation, the EC 50 was lower for VINS compared to BHARAT - 60 μg/mL vs. EC 50 of both antivenoms was only slighty different for E.

In binding studies EC 50 for all VINS antivenoms were less than BHARAT for D. Efficacy was compared statistically for one batch from each manufacturer where multiple vials were available. In vitro efficacy was tested at venom concentrations consistent with human envenoming.

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.

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