Research on epidemiology of toxin-based diseases (TBDs) (other than microbial toxin diseases) has long been an area of patchy development, with a few areas undertaking extensive quality research, while many others have fragmentary, unsatisfactory, or virtually non-existent research in this field. This may reflect the reality that TBDs are not a focus for the historic professional groups within medicine, which originated mainly in western communities in Europe, where TBDs are mostly uncommon to rare.
From available research over the last 100 or so years we now know that TBDs are, in fact, an important disease group globally, most notably in the rural tropics and poor communities from the Americas, through Africa, the middle-east and across Asia to the Pacific. Problem TBDs include those caused by both venoms (such as snakebite and scorpion sting) and poisons (such as fugu, ciguatera, and shellfish poisoning).
With climate change, specifically general warming, particularly of oceans, marine poisoning TBDs appear of increasing global importance, especially varieties of shellfish poisoning. These are now affecting developed-world countries such as European nations bordering the Mediterranean Sea. Consequently this group of TBDs is receiving more research attention and so progressively moving out of the “neglected” category.
The rise in development of clinical toxinology as an area of specific medical expertise, over the last 15 years, coincident with the establishment of the international short course in clinical toxinology in 1997 (and still running today), has seen a burgeoning of interest in TBDs and, more particularly, venom-based diseases (VBDs). VBDs such as snakebite have benefitted from the attention of noted researchers and an increasing number of useful epidemiologic and other studies are emerging. For snakebite this has allowed better delineation of the global extent of the problem, resulting in convincing the World Health Organisation (WHO) to devote some resources to this area and declare snakebite a “neglected tropical disease”. WHO has also sponsored development of universal guidelines for antivenom production that should now be used by all antivenom producers to guide their production processes and the expected quality of their products.
It is tragic that India, arguably the nation with the highest toll from VBDs such as snakebite, has historically devoted so little effort to managing these VBDs. The most recent quality epidemiologic research from India indicates in excess of 45,000 Indians die from snakebite every year. The likely number with significant morbidity following snakebite will be far higher. This is an enormous human, social and economic toll on India.
Indian antivenoms (locally and, in my view, inappropriately named “anti snake venom” (ASV)) are available, but of variable quality. More importantly, it appears the Indian health workers are, in general, inadequately trained in the diagnosis and treatment of snakebite and related VBDs. Providing antivenom is not a sufficient response to improving outcomes for snakebite patients. Unless health workers both understand and are prepared to treat snakebite, and are resourced to do so, significant improvements in outcome are unlikely. This requires an ongoing training program. This has been proposed and, on occasion in some locales, actually implemented in recent times, but really requires a whole-of-government commitment and effort and utilisation of actual experts in clinical toxinology to assist in development and deployment of a training system. It is notable that so far, despite invitations, no Indian doctor has attended the Clinical Toxinology Short Course, while a number of doctors from adjacent nations have done so.
It is my understanding, after both reading papers on snakebite from India, and discussing issues with Indian doctors, that antivenom is underused in India because health workers are afraid of treating snakebite and especially afraid of adverse reactions to antivenom. The prime reason for this is inadequate training on the diagnosis and management of snakebite. This needs to be addressed by a national and ongoing training scheme. The secondary reason for reluctance to use antivenom is the quality of the antivenom. Antivenoms made with older standard methods can be associated with high rates of major adverse reactions. Historically Indian antivenoms have been considered as likely to cause major adverse reactions. Modern methods for making antivenoms decrease the likelihood of major adverse reactions to a low rate. It appears that Indian antivenom producers have not accepted these procedures universally.
Snakes are just one type of venomous animal and amongst venomous snakes there are many species and many different venoms and clinical effects. Research into snakebite and antivenom use in another part of the world may not apply to snakebite in India. It is very important that Indian health workers and officials do not take information published by these foreign researchers and assume it applies to India. That is where the expertise of a specialist trained clinical toxinologist is vital, to interpret research and advise on applicability (or not) to India.
Globally there is a wealth of experience with use of antivenom to treat VBDs, particularly snakebite, and most of that experience indicates the positive roll antivenom has in improving patient outcomes. A few, often controversial studies, outside of India, have shown data that antivenom in those particular, non-Indian, circumstances, may not be effective for certain forms of envenoming. Only by undertaking careful research in India, with Indian snakes and antivenoms, in large prospective clinical studies, can we develop knowledge of antivenom effectiveness in the specific Indian setting.
We do already know that Indian antivenoms do not cover all the important venomous snakes and that even for the snakes covered, the methods of production will likely cause deficiencies in coverage. It is essentially to use a venom from geographically diverse sources to make the snake anti-venom effective throughout the nation. Current regulations in India about who can supply snake venom and from where make it difficult or impossible to provide such geographically diverse venom for antivenom production.
These antivenoms almost certainly could be improved further, using new technologies, that may not increase the cost of production. Equally importantly, the coverage of the antivenoms is not ideal and misses some important species such as hump nosed vipers. A better venom immunising mix would allow better coverage for antivenoms, but to obtain this better immunising mix may require changes in government policy about who and how venoms are supplied.
Antivenom can be a very important part of treating snakebite, but it is not the only treatment. A patient with snakebite-induced paralysis may not respond to antivenom, because of the way the venom works. This is not a failure of the antivenom product, but just a reality of venom action. To survive the patient needs external respiratory support and if this is provided effectively, full recovery is likely. Similarly, if venom damages kidneys, temporary support of kidney function is needed and with this most patients should make a full recovery.
It is difficult for a non-Indian doctor to assess how snakebite is rated within the Indian health system. Evidence suggests that, at least in the past, it was an underrated and largely forgotten problem. This may still be the case, but I cannot be sure if changes are already occurring in government policy and action that might change this situation in the future.
The clinicians in this toxinology community, such as myself, remain most interested in assisting India and Indians to develop an effective response to reduce this snakebite toll, but we need to be asked to help by India and Indians, starting at the national government level, but also involving ordinary Indian health workers. It is these health workers who hold the key to improving outcomes for Indian snakebite patients. It is they who ultimately and into the future must deliver care to these patients. We need to empower them to do so effectively and with confidence born from proper training and adequate resourcing. At the same time as improving treatment of bitten patients, every effort should be made to improve prevention, to reduce the number of patients with snakebite.
Prof. Julian White MB, BS, MD, FACTM
Consultant Clinical Toxinologist
Director, Clinical Toxinology Short Course
Head of Toxinology
Women’s & Children’s Hospital
North Adelaide, Australia
Related Links : Clinical Toxinology Resources (http://www.toxinology.com )
Note : This is the full text of an e-mailed interview of Prof White conducted in 2013 .
