About Snakebite

         Venomous snakes could deliver a complex mixture of venom proteins through the highly specialised fang to cause snakebite envenomation. The envenomation by venomous snakes can lead to severe clinical complications and possibly cause death. As snakebite envenomation mainly affects poor community resided rural areas, it has been called as a “disease of poverty” and is listed as a neglected tropical disease by World Health Organisation. This issue poses serious public health threats in many parts of the world, particularly developing and under-developed countries in the tropics and subtropics. Worldwide, it is approximately 5.5 million snakebite cases occur annually, resulting in close to 2 million envenomation with close to a hundred thousand fatalities, besides an unknown percentage of survivors who continue to suffer permanent physical disability due to local tissue destruction. In Southeast Asia, snake envenomation affects not only rural and agricultural populations, but also those living near the cities as humans are encroaching into the habitats of snakes following rapid urbanization, including Malaysia, a tropical country rich in biodiversity. Among the many venomous snakes in this region, the commonest biter comprises three main subfamilies of snakes: Elapinae (cobras, king cobra, kraits, and coral snakes), Hydrophinae (sea snakes), and Crotalinae (pit vipers). These snake species are classified as medically dangerous snakes due to the capability of delivering large quantity of lethal venom.

Snake Venom

          Snake venoms consist mainly of proteins and peptides (>90%) that exhibit diverse biochemical and pharmacological activities. Venom represents a trophic adaptive trait, and is unique among species. The complexity of venom develops through a series of evolutionary events that include repeated gene duplication and molecular adaptation, leading to protein neofunctionalization to suit the toxin roles in predation, digestion and defence. The major contents and biochemical activities of venoms from phylogenetically closely related species generally share a similar pattern; for example the predominance of muscle-paralysing neurotoxins (alpha-, beta- and kappa-neurotoxin) in the venoms of most elapid snakes. Nevertheless, venom composition (toxin subtypes and relative abundances) can vary remarkably between congeneric or even intraspecific species as a result of differences in their ecological niche and the consequent genetic adaptation. The implication of this phenomenon is medically relevant, as diverse toxin composition can lead to varied envenoming effects and treatment outcome, where antivenom’s action is usually species-specific.

It is known that in Southeast Asia, many countries depend on antivenom supply from non-domestic manufacturers that use immunogens from species non-native to the importing countries. This poses a question of how appropriate or effective the antivenoms are for heterologous or non-native species, considering the various reports on geographical venom variations. Since antivenom is the only definitive treatment for snake envenomation, essentially, the effectiveness of venom neutralization relies on the molecular characteristics and antigenic determinants of the venom toxins. Considerable compositional, syndromic and immunological variations have been reported for the venoms of several cobra taxa, including those which are sympatric.

Snakebite Envenomation

          In snakebite envenomation, the clinical presentation of a patient represents a complex syndrome resulted from the body responses to the pharmacological actions of different components in snake venom. Venom toxic effects have often been conveniently classified as neurotoxic, hemotoxic, cardiotoxic, nephrotoxic, myotoxic, etc. based on the predominant clinical effect of particular venom. Organ- or system-based descriptions as such receive criticism at times that the classification oversimplifies the complexity of venom effects and does not represent the interaction of various toxins on tissues of different organs. Nonetheless, the descriptions suggest the prominent clinical syndrome of particular snakebite and hence have a practical value in management, for instance, the preparation of intubation equipment, blood products for transfusion, and dialysis facility in anticipation of the likely pathological outcome from the bite of a particular species. On the other hand, laboratory characterizations of venom toxicities can never be oversimplified, and it demands multiple disciplinary approaches, involving both in vitro and in vivo techniques.

Medically Important Snakes in Malaysia

          Medically important snakes in Malaysia largely originate from the Elapidae family and the Crotalinae subfamily. Venoms of many elapid snakes (cobra, krait and sea snakes) generally produce flaccid paralysis and respiratory difficulty leading to asphyxia. Elapid venoms mainly contain proteins/peptides of low to moderate molecular mass (<15 kDa), with one key group called the three-finger toxins (6-8 kDa), which include various neurotoxins and cytotoxins (or cardiotoxins). On the other hand, crotalid venoms constitute moderate to high molecular mass proteins (>15 kDa), many of which are enzymes, e.g., thrombin-like serine proteases, metalloproteinases, L-amino acid oxidases, etc. However, phospholipases A2 present usually in substantial amount in both the elapid and crotalid venoms. The envenoming effect of elapid bites usually develops rapidly, and death can ensue within hours. In contrast to rapid neuromuscular paralysis by the elapids, pit viper bites tend to develop more insidious and manifest more often as hemorrhage and coagulopathy. With the advancement in molecular phylogenetics in the last two decades, the taxonomy of many medically important snakes including those in Malaysia has been extensively revised, making interpretation of findings from earlier works difficult. The importance of development in snake systematics, however, cannot be overlooked in the field of medical toxinology, as venom compositions often vary extensively even between very closely related species or subspecies, resulting in a diverse presentation of envenoming effects and inconsistent therapeutic response to antivenom therapy.