Wspólnotowy Serwis Informacyjny Badan i Rozwoju - CORDIS

Periodic Report Summary 1 - BITES (Biodiversity Informatics and Technology Exchange for Snakebite management)

Globally, India tops the list of countries with the highest annual incidence of snakebite. Although the “Big Four” species (comprising two elapid and two viper species) are thought to cause the highest number of envenomations in India, some pitviper bites may also be lethal, and many species are a major occupational hazard for plantation workers in certain regions. The population being predominantly rural, a considerable number of bite victims either die or are permanently disabled and suffer considerable economic losses. Reduction of snakebite mortality and morbidity requires a multidisciplinary approach and concerted effort between experts in different fields because the efficient medical management of snakebites requires timely administration of appropriate antivenins that neutralize toxins. As venom compositions are species-specific, this is dependent on a comprehensive understanding of the diversity and geographic distribution of venomous snakes, and regional toxin variation. Some studies on regional venom variation have shown the use of a single polyvalent anti-venin to be ineffective even among cases of the “Big Four” species, and there have been no studies investigating the link between venomous snake systematics and regional venom variation. Additionally, there is evidence for the presence of cryptic diversity in some groups. These issues have serious implications for toxinological and antivenom research and have confounded the effective management of snake bite in India.

Getting the taxonomy right is an acknowledged key component in the development of a strategy for the improvement of the snakebite situation by the Global Snakebite Initiative and is also important for conservation and basic ecological and biochemical research, with the venoms representing a treasure trove of bioactive substances with potential pharmaceutical applications. Another necessary step towards improving the snakebite problem is to improve the epidemiological knowledge of snakebite incidence and causal species in different regions. Diagnosis of the species responsible also has clinical importance as it may prevent the unnecessary administration of antivenom, with its attendant risks of adverse reactions, in the case of bites by non-venomous species, or species against whose venom the current antivenoms are known to be ineffective. While immunoassays have been successfully used for diagnosis in other parts of the world (e.g., Australia), they are less likely to be useful in the Indian context where high species diversity, cross-reactivity between venoms of some species and within-species venom variation in others are known limitations. Investigation of the potential of bite-site swabs for PCR-based diagnosis of snake species responsible has shown to be possible and will be useful at least in the gathering of epidemiological data. Some issues remain to be addressed about potential biases in the data collected. Proteomic tools enable a robust knowledge of venom composition and of the onset of ontogenetic, individual, and geographic venom variability which may impact the treatment of bite victims and the selection of specimens for the generation of improved antidotes. Developing toxin-specific antibodies to improve antivenom dose-efficacy is critically dependent upon a detailed knowledge of the venom toxin profile, and proteomic-based tools developed for exploring venom proteomes and the design of the best venom mixtures for immunisation will provide key information for increasing the effectiveness of antivenoms. Proteomics tools also offer the possibility of establishing the cross-reactivity of existing antivenoms and in this project “second-generation” immunoaffinity antivenomics strategies allowing better resolution and a more accurate quantification of results will be implemented.

Some medically significant snake venom toxin families (such as snake venom metalloproteinases or SVMPs) are subjected to extensive post-translational modifications which contribute to the complexity of the venom proteomes. Transcriptomic studies thus can give a more accurate snapshot of the total toxin content and diversity, similarities and differences among snakes of different seasons, geographic origin, age class or gender, which might be significant in informing the strategy of sampling venom for antivenom manufacture and opens the door for the transcriptome-based design of synthetic multi-epitope DNA immunogens to develop toxin-specific antivenoms with wide geographic and snake-species coverage. However, the difficulty in obtaining permits to sacrifice highly protected snake species in India currently inhibits adopting this approach. In this work package, we will investigate and validate the use of non-invasive quantitative PCR amplification of stable mRNA in expressed venom recently described for profiling the transcriptomic variation in snake species.

Current legislation within India severely restricts acquisition and export of samples for study in other countries, and thus the problem needs to be addressed using the facilities, expertise, and well-equipped laboratories within Indian research institutions. However, as most venomous snake species have at least part of their ranges, or have close relatives, outside the political boundaries of India, it is also necessary for Indian researchers to work with international counterparts. Hence this programme is intended to facilitate exchange of information and establishment of complementary protocols and analysis techniques for future collaboration between taxonomists, molecular biologists, protein biologists and herpetologists based in the EU and India. We also planned to organise workshops to transfer relevant technology, knowledge, best practices and skills in relevant sub-disciplines to early stage researchers in India: however, budgetary limitations means that these have been reduced in number. The first, key, step in achieving the objectives is to obtain the appropriate tissue and venom samples from key regions of the country as this is not something that can be bought from a biological supply company. The project has experienced delays due to changes in institutions involved in both the EU and India which held up signing the partnership agreement, without which no applications could be made. However, appropriate contacts were made to facilitate permit applications, currently pending. Alternative sources of material for training purposes have also been sourced and the planned exchanges have been re-scheduled to make up for time lost.

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United Kingdom


Life Sciences
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