Snakebite and Envenomation Management in Malaysia

Venomics of Trimeresurus (Popeia) nebularis, the Cameron Highlands Pit Viper from Malaysia: Insights into Venom Proteome, Toxicity and Neutralization of Antivenom

“…The potency values of GPVAV (interpreted as the amount of venom completely neutralized by a unit volume or a unit mass of antivenom) were considerably high (P = 1.6 mg venom per mL antivenom or normalized potency, n-P = 79.2 mg venom per g antivenom). It is theoretically possible to extrapolate that in T. nebularis bite, a total of 30 mg of venom injected and systematically absorbed can be completely neutralized by 20–30 mL of GPVAV (equivalent to 2–3 vials of antivenom), which appears to concur with the initial dose of GPVAV recommended in clinical guidelines [ 19 , 20 ]. Nonetheless, from the practical standpoint, the dosing of GPVAV should be determined and optimized clinically, as the neutralization effect of antivenom is modulated by complex pharmacokinetics of both venom and antivenom proteins in in vivo system.…”

“…Nonetheless, in many Southeast Asian countries including Malaysia, this syndromic divergence is not clear-cut and non-specific, as many Trimeresurus sp. including T. nebularis , like C. rhodostoma , do cause thrombocytopenia besides hemorrhage in envenoming [ 20 , 37 ]. The overall hemotoxic syndrome is a constellation of effects induced by the abundant SVMP hemorrhagins, platelet-disrupting snaclecs and other coagulopathic toxins (such a SVSP and disintegrins discussed below) in their venoms.…”

“…The distribution of T. nebularis causes endemic problem of snakebite envenomation in the montane area of central Malaysia, notably in Cameron Highlands where agricultural activities and eco-tourism are common [ 19 ]. Although formal epidemiological report is lacking, hospital records and data collected by the Remote Envenomation Consultancy Service team (RECS, Malaysia) revealed that T. nebularis bite is one of the leading causes of envenoming in the affected area, resulting in hemorrhagic syndrome and coagulopathy [ 20 ]. As there is no species-specific antivenom available for T. nebularis , the hetero-specific Thai Green Pit Viper Antivenom (GPVAV, raised against the venom of Trimeresurus albolaris , or Cryptelytrops albolabris ) has been used empirically in recent years to treat T. nebularis envenoming and this approach has been anecdotally reported to be effective based on unpublished clinical observation from the Remote Envenomation Consultancy Service team in the country [ 19 ].…”

In Vitro Immunological Cross-Reactivity of Thai Polyvalent and Monovalent Antivenoms with Asian Viper Venoms

“…However, the presence of Russell's viper has not been reported in Peninsular Malaysia nor Borneo [29]. Additionally, envenoming by less studied "green pit vipers" such as the mangrove pit viper (T. purpureomaculatus), Hagen's pit viper (T. hageni), and the Siamese Peninsular pit viper (T. fucatus: former known as Popeia fucata) have been shown to cause severe bleeding disorders and tissue necrosis, resulting in amputation [30]. Since there is no antivenom manufacturer in Malaysia, most antivenom is currently imported from Thailand, yet a comprehensive understanding of the interaction of these antivenoms with Malaysian snake venoms is lacking.…”

“…To investigate whether the high levels of binding observed between the HPAV polyvalent antivenom, and to a lesser extent the monovalent antivenoms, and Malaysian snake venoms result in any form of venom neutralization, we used an in vitro venom coagulation assay. This is relevant because clinical outcomes observed following envenoming by Asian pit vipers include systemic coagulopathy and hemorrhage, as well as progressive edema and local tissue necrosis, which can result in amputation of the affected digit or limb [22,30,32,33]. It has been postulated that venom thrombin-like serine protease (SVSP) and snake venom metalloproteinase (SVMP) toxins play an important role in causing the coagulopathy observed following envenomings by pit vipers [33,34].…”