Evaluation of the geographical utility of Eastern Russell’s viper (Daboia siamensis) antivenom from Thailand and an assessment of its protective effects against venom-induced nephrotoxicity

Abstract

AbstractBackgroundDaboia siamensis(Eastern Russell’s viper) is a medically important snake species found widely distributed across Southeast Asia. Envenomings by this species can result in systemic coagulopathy, local tissue injury and/or renal failure. While administration of specific antivenom is an effective treatment for Russell’s viper envenomings, the availability of, and access to, geographically-appropriate antivenom remains problematic in many rural areas. In this study, we determined the binding and neutralizing capability of antivenoms manufactured by the Thai Red Cross in Thailand againstD. siamensisvenoms from three geographical locales: Myanmar, Taiwan and Thailand.Methodology/ Principle findingsTheD. siamensismonovalent antivenom displayed extensive recognition and binding to proteins found inD. siamensisvenom, irrespective of the geographical origin of those venoms. Similar immunological characteristics were observed with the Hemato Polyvalent antivenom, which also usesD. siamensisvenom as an immunogen, but binding levels were dramatically reduced when using comparator monovalent antivenoms manufactured against different snake species. A similar pattern was observed when investigating neutralization of coagulopathy, with the procoagulant action of all three geographical venom variants neutralized by both theD. siamensismonovalent and the Hemato Polyvalent antivenoms, while the comparator monovalent antivenoms were ineffective. Assessments ofin vivonephrotoxicity revealed thatD. siamensisvenom (700 µg/kg) significantly increased plasma creatinine and blood urea nitrogen levels in anaesthetised rats. The intravenous administration ofD. siamensismonovalent antivenom at three times higher than the recommended scaled therapeutic dose, prior to and 1 h after the injection of venom, resulted in reduced levels of markers of nephrotoxicity, although lower doses had no therapeutic effect.Conclusions/SignificanceThis study highlights the potential broad geographical utility of the ThaiD. siamensismonovalent antivenom for treating envenomings by the Eastern Russell’s viper. However, only the early delivery of high antivenom doses appear capable of preventing venom-induced nephrotoxicity.Author summarySnakebite is a major public health concern in rural regions of the tropics. The Eastern Russell’s viper (Daboia siamensis) is a medically important venomous snake species that is widely distributed in Southeast Asia and Southern China, including Taiwan. Envenoming byD. siamensiscauses several systemic pathologies, most notably acute kidney failure and coagulopathy. The administration of antivenom is the mainstay therapeutic for treating snakebite, but in remote areas of Myanmar and Southern China access to antivenom is limited, and can result in the use of inappropriate, non-specific, antivenoms and treatment failure. Therefore, maximizing the utility of available efficacious antivenom is highly desirable. In this study, we investigated the utility of the widely available Thai Red Cross antivenoms for binding to and neutralizingD. siamensisvenoms sourced from three distinct locales in Asia. Since the effectiveness and antivenom dose required to preventD. siamensisvenom-induced nephrotoxicity has been controversial, we also examined the preclinical efficacy ofD. siamensisantivenom at preventing this pathology in experimentally envenomed anaesthetised animals. Our findings suggest that monovalent antivenom from Thailand, which is clinically effective in this country, has highly comparable levels of immunological binding andin vitroneutralization toD. siamensisvenoms from Taiwan and Myanmar. We also show that the early administration of high therapeutic doses of antivenom are likely required to neutralize nephrotoxins and thus prevent acute renal failure following envenoming. Our findings suggest that certain Thai Red Cross antivenoms likely have wide geographical utility againstD. siamensisvenom and therefore may be useful tools for managing snakebite envenomings by this species in the absence of available locally manufactured therapeutics.