In-vitro Neurotoxicity of Two Malaysian Krait Species (Bungarus candidus and Bungarus fasciatus) Venoms: Neutralization by Monovalent and Polyvalent Antivenoms from Thailand

Abstract

Bungarus candidus and Bungarus fasciatus are two species of krait found in Southeast Asia. Envenoming by these snakes is often characterized by neurotoxicity and, without treatment, causes considerable morbidity and mortality. In this study, the in vitro neurotoxicity of each species, and the effectiveness of two monovalent antivenoms and a polyvalent antivenom, against the neurotoxic effects of the venoms, were examined in a skeletal muscle preparation. Both venoms caused concentration-dependent inhibition of indirect twitches, and attenuated responses to exogenous nicotinic receptor agonists, in the chick biventer preparation, with B. candidus venom being more potent than B. fasciatus venom. SDS-PAGE and western blot analysis indicated different profiles between the venoms. Despite these differences, most proteins bands were recognized by all three antivenoms. Antivenom, added prior to the venoms, attenuated the neurotoxic effect of the venoms. Interestingly, the respective monovalent antivenoms did not neutralize the effects of the venom from the other Bungarus species indicating a relative absence of cross-neutralization. Addition of a high concentration of polyvalent antivenom, at the t90 time point after addition of venom, partially reversed the neurotoxicity of B. fasciatus venom but not B. candidus venom. The monovalent antivenoms had no significant effect when added at the t90 time point. This study showed that B. candidus and B. fasciatus venoms display marked in vitro neurotoxicity in the chick biventer preparation and administration of antivenoms at high dose is necessary to prevent or reverse neurotoxicity.

Variations in neurotoxicity and proteome profile of Malayan krait (Bungarus candidus) venoms

“…However, when BCAV at 3x recommended titer was added at the t 90 time point, it failed to restore indirect twitches. The inability of antivenom to reverse neurotoxicity is in agreement with previous in-vitro studies [13], and indicates the likely presence of irreversible presynaptic neurotoxins in the venoms [36]. It is also possible that there are unique toxins in BC-M and BC-I which unable to be neutralized by the antivenom.…”

“…In the present study, B . candidus venoms were found to be more potent compared to the venoms from known neurotoxic elapids previously characterized using the same chick-biventer cervicis nerve-muscle preparation in our laboratory (Table 1) [13,28,29]. However, there were no significant differences in neurotoxicity between B .…”

“…fasciatus antivenom is not effective in preventing B . candidus -induced in vitro neurotoxicity [13]. Unfortunately, there is no literature in the database on in vivo study of BCAV and its efficacy compared with NPAV.…”

“…Although B . fasciatus monovalent antivenom (BFAV) has been shown to have neutralizing effects against three specific kraits found in Thailand [12], neither BFAV nor BCAV cross neutralized the in-vitro skeletal muscle effects of venoms from other Bungarus species [13]. In addition, administration of antivenom at a higher concentration than recommended was required to prevent in-vitro neurotoxic activity [13].…”

Allergic reactions to antivenom in a patient bitten twice by the same snake within a month: A rare case report and literature review

“…Even if the commercial monovalent antivenom in Australia is still polyvalent. 19 Anti snake venom serum of various types of antibodies, more or less residual Fc fragments, which for the human body is a heterologous substance, which caused the occurrence of allergic reactions is reasonable. Some studies showed that it may be feasible to reduce adverse reactions using antivenom prepared with highly immunogenic venom components that produce neutralizing and protective antibody after immunizing animals.…”