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

Abstract

BackgroundDaboia siamensis (Eastern Russells 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 Russells 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 against D. siamensis venoms from three geographical locales: Myanmar, Taiwan and Thailand.\n\nMethodology/ Principle findingsThe D. siamensis monovalent antivenom displayed extensive recognition and binding to proteins found in D. siamensis venom, irrespective of the geographical origin of those venoms. Similar immunological characteristics were observed with the Hemato Polyvalent antivenom, which also uses D. siamensis venom 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 the D. siamensis monovalent and the Hemato Polyvalent antivenoms, while the comparator monovalent antivenoms were ineffective. Assessments of in vivo nephrotoxicity revealed that D. siamensis venom (700 {micro}g/kg) significantly increased plasma creatinine and blood urea nitrogen levels in anaesthetised rats. The intravenous administration of D. siamensis monovalent 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.\n\nConclusions/SignificanceThis study highlights the potential broad geographical utility of the Thai D. siamensis monovalent antivenom for treating envenomings by the Eastern Russells viper. However, only the early delivery of high antivenom doses appear capable of preventing venom-induced nephrotoxicity.\n\nAuthor summarySnakebite is a major public health concern in rural regions of the tropics. The Eastern Russells viper (Daboia siamensis) is a medically important venomous snake species that is widely distributed in Southeast Asia and Southern China, including Taiwan. Envenoming by D. siamensis causes 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 neutralizing D. siamensis venoms sourced from three distinct locales in Asia. Since the effectiveness and antivenom dose required to prevent D. siamensis venom-induced nephrotoxicity has been controversial, we also examined the preclinical efficacy of D. siamensis antivenom 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 and in vitro neutralization to D. siamensis venoms 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 against D. siamensis venom and therefore may be useful tools for managing snakebite envenomings by this species in the absence of available locally manufactured therapeutics.