Antivenom Cross-Neutralization of the Venoms of Hydrophis schistosus and Hydrophis curtus, Two Common Sea Snakes in Malaysian Waters

Abstract

Sea snake envenomation is a serious occupational hazard in tropical waters. In Malaysia, the beaked sea snake (Hydrophis schistosus, formerly known as Enhydrina schistosa) and the spine-bellied sea snake (Hydrophis curtus, formerly known as Lapemis curtus or Lapemis hardwickii) are two commonly encountered species. Australian CSL sea snake antivenom is the definitive treatment for sea snake envenomation; it is unfortunately extremely costly locally and is not widely available or adequately stocked in local hospitals. This study investigated the cross-neutralizing potential of three regionally produced anti-cobra antivenoms against the venoms of Malaysian H. schistosus and H. curtus. All three antivenoms conferred paraspecific protection from sea snake venom lethality in mice, with potency increasing in the following order: Taiwan bivalent antivenom < Thai monocled cobra monovalent antivenom < Thai neuro polyvalent antivenom (NPAV). NPAV demonstrated cross-neutralizing potencies of 0.4 mg/vial for H. schistosus venom and 0.8 mg/vial for H. curtus, which translates to a dose of less than 20 vials of NPAV to neutralize an average amount of sea snake venom per bite (inferred from venom milking). The cross-neutralization activity was supported by ELISA cross-reactivity between NPAV and the venoms of H. schistosus (58.4%) and H. curtus (70.4%). These findings revealed the potential of NPAV as a second-line treatment for sea snake envenomation in the region. Further profiling of the cross-neutralization activity should address the antivenomic basis using purified toxin-based assays.

Venomics of the beaked sea snake, Hydrophis schistosus: A minimalist toxin arsenal and its cross-neutralization by heterologous antivenoms

“…Based on the proteomic findings, the toxin diversity of H. schistosus venom appears rather limited compared to some of its terrestrial elapidic relatives, such as cobras [31,32,34,36], king cobra [44] and kraits [33], which venom proteomes exhibit well beyond 30 proteins classified into at least 10 protein families. In addition, like many hydrophiids, the venom of H. schistosus is usually injected in a small concentrated amount yet capable of producing severe toxicity [14,21,37]. The findings of such "minimalist adapatation" in a snake venom with low molecular diversity but high toxic concentration is in agreement with the economy of toxin arsenal as an evolutionary solution convergently adopted by most hydropiids.…”

“…To date, the only indicated antivenom for the treatment of H. schistosus envenomation is the CSL Sea Snake Antivenom manufactured by the Australian Commonwealth Serum Laboratory [4]; this product however is extremely costly in Southeast Asia (a retail price of close to RM 20,000 or USD 5,000 per vial), demanding stringent cold-chain transport and storage, and is not widely available or adequately stocked in local hospitals [21]. Nonetheless, cross-neutralization of this venom in mice lethality study by other elapid antivenoms such as Thai cobra antivenoms had been reported, presumably due to the presence of common epitopes between the venoms [21][22][23]. A detailed profiling of H. schistosus venom and assessment of antivenom cross-neutralization of individual toxins remain to be explored.…”

“…The method was adapted from Tan et al [21]: In vivo neutralization study was carried out with independent administration of toxin and antivenom: 2.5 LD 50 of the venom toxin was administered by subcutaneous (s.c.) injection into mice (20-25g, n=4), followed by intravenous (i.v.) injection of appropriately diluted antivenom (NKMAV or NPAV, in a total volume of 200 µL) 10 min post-envenomation.…”

Venom and Purified Toxins of the Spectacled Cobra (Naja naja) from Pakistan: Insights into Toxicity and Antivenom Neutralization

“…Mice used in this study were of albino Institute of Cancer Research (ICR) strain (20)(21)(22)(23)(24)(25) 18 pipette tips were purchased from Merck Millipore (Billerica, MA). Resource S (1 mL) column was purchased from GE Healthcare (Stockholm, Sweden).…”

“…The determination of intravenous (IV) and subcutaneous (SC) median lethal dose for venom or toxin was modified from an in vivo assay reported recently from the same laboratory. 23 The venom or toxins were injected IV (via tail caudal vein) or SC (via loose skin over the neck) into albino mice of ICR strain (20-25 g) at appropriate doses (N = 4 per dose). The mice were allowed free access to food and water ad libitum, and the survival ratio of mice at each dose was recorded at 48 hours post injection.…”